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Chemical Structure| 403-42-9 Chemical Structure| 403-42-9

Structure of 4'-Fluoroacetophenone
CAS No.: 403-42-9

Chemical Structure| 403-42-9

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Product Citations

Product Citations

Siriboe, Mary G ; Vargas, David A ; Fasan, Rudi ;

Abstract: Chiral cyclopropanols are highly desirable building blocks for medicinal chemistry, but the stereoselective synthesis of these molecules remains challenging. Here, a novel strategy is reported for the diastereo- and enantioselective synthesis of cyclopropanol derivatives via the biocatalytic asymmetric cyclopropanation of vinyl esters with ethyl diazoacetate (EDA). A dehaloperoxidase enzyme from Amphitrite ornata was repurposed to catalyze this challenging cyclopropanation reaction, and its activity and stereoselectivity were optimized via protein engineering. Using this system, a broad range of electron-deficient vinyl esters were efficiently converted to the desired cyclopropanation products with up to 99.5:0.5 diastereomeric and enantiomeric ratios. In addition, the engineered dehaloperoxidase-based biocatalyst is able to catalyze a variety of other abiological carbene transfer reactions, including N?H/S?H carbene insertion with EDA as well as cyclopropanation with diazoacetonitrile, thus adding to the multifunctionality of this enzyme and defining it as a valuable new scaffold for the development of novel carbene transferases.

Alternative Products

Product Details of [ 403-42-9 ]

CAS No. :403-42-9
Formula : C8H7FO
M.W : 138.14
SMILES Code : C1=CC(=CC=C1C(C)=O)F
MDL No. :MFCD00000354
InChI Key :ZDPAWHACYDRYIW-UHFFFAOYSA-N
Pubchem ID :9828

Safety of [ 403-42-9 ]

GHS Pictogram:
Signal Word:Warning
Hazard Statements:H315-H319-H335
Precautionary Statements:P261-P305+P351+P338

Computational Chemistry of [ 403-42-9 ] Show Less

Physicochemical Properties

Num. heavy atoms 10
Num. arom. heavy atoms 6
Fraction Csp3 0.12
Num. rotatable bonds 1
Num. H-bond acceptors 2.0
Num. H-bond donors 0.0
Molar Refractivity 36.59
TPSA ?

Topological Polar Surface Area: Calculated from
Ertl P. et al. 2000 J. Med. Chem.

17.07 ?2

Lipophilicity

Log Po/w (iLOGP)?

iLOGP: in-house physics-based method implemented from
Daina A et al. 2014 J. Chem. Inf. Model.

1.74
Log Po/w (XLOGP3)?

XLOGP3: Atomistic and knowledge-based method calculated by
XLOGP program, version 3.2.2, courtesy of CCBG, Shanghai Institute of Organic Chemistry

1.72
Log Po/w (WLOGP)?

WLOGP: Atomistic method implemented from
Wildman SA and Crippen GM. 1999 J. Chem. Inf. Model.

2.45
Log Po/w (MLOGP)?

MLOGP: Topological method implemented from
Moriguchi I. et al. 1992 Chem. Pharm. Bull.
Moriguchi I. et al. 1994 Chem. Pharm. Bull.
Lipinski PA. et al. 2001 Adv. Drug. Deliv. Rev.

2.21
Log Po/w (SILICOS-IT)?

SILICOS-IT: Hybrid fragmental/topological method calculated by
FILTER-IT program, version 1.0.2, courtesy of SILICOS-IT, http://www.silicos-it.com

2.58
Consensus Log Po/w?

Consensus Log Po/w: Average of all five predictions

2.14

Water Solubility

Log S (ESOL):?

ESOL: Topological method implemented from
Delaney JS. 2004 J. Chem. Inf. Model.

-2.16
Solubility 0.96 mg/ml ; 0.00695 mol/l
Class?

Solubility class: Log S scale
Insoluble < -10 < Poorly < -6 < Moderately < -4 < Soluble < -2 Very < 0 < Highly

Soluble
Log S (Ali)?

Ali: Topological method implemented from
Ali J. et al. 2012 J. Chem. Inf. Model.

-1.69
Solubility 2.79 mg/ml ; 0.0202 mol/l
Class?

Solubility class: Log S scale
Insoluble < -10 < Poorly < -6 < Moderately < -4 < Soluble < -2 Very < 0 < Highly

Very soluble
Log S (SILICOS-IT)?

SILICOS-IT: Fragmental method calculated by
FILTER-IT program, version 1.0.2, courtesy of SILICOS-IT, http://www.silicos-it.com

-2.98
Solubility 0.144 mg/ml ; 0.00104 mol/l
Class?

Solubility class: Log S scale
Insoluble < -10 < Poorly < -6 < Moderately < -4 < Soluble < -2 Very < 0 < Highly

Soluble

Pharmacokinetics

GI absorption?

Gatrointestinal absorption: according to the white of the BOILED-Egg

 High
BBB permeant?

BBB permeation: according to the yolk of the BOILED-Egg

 Yes
P-gp substrate?

P-glycoprotein substrate: SVM model built on 1033 molecules (training set)
and tested on 415 molecules (test set)
10-fold CV: ACC=0.72 / AUC=0.77
External: ACC=0.88 / AUC=0.94

 No
CYP1A2 inhibitor?

Cytochrome P450 1A2 inhibitor: SVM model built on 9145 molecules (training set)
and tested on 3000 molecules (test set)
10-fold CV: ACC=0.83 / AUC=0.90
External: ACC=0.84 / AUC=0.91

 Yes
CYP2C19 inhibitor?

Cytochrome P450 2C19 inhibitor: SVM model built on 9272 molecules (training set)
and tested on 3000 molecules (test set)
10-fold CV: ACC=0.80 / AUC=0.86
External: ACC=0.80 / AUC=0.87

 No
CYP2C9 inhibitor?

Cytochrome P450 2C9 inhibitor: SVM model built on 5940 molecules (training set)
and tested on 2075 molecules (test set)
10-fold CV: ACC=0.78 / AUC=0.85
External: ACC=0.71 / AUC=0.81

 No
CYP2D6 inhibitor?

Cytochrome P450 2D6 inhibitor: SVM model built on 3664 molecules (training set)
and tested on 1068 molecules (test set)
10-fold CV: ACC=0.79 / AUC=0.85
External: ACC=0.81 / AUC=0.87

 No
CYP3A4 inhibitor?

Cytochrome P450 3A4 inhibitor: SVM model built on 7518 molecules (training set)
and tested on 2579 molecules (test set)
10-fold CV: ACC=0.77 / AUC=0.85
External: ACC=0.78 / AUC=0.86

 No
Log Kp (skin permeation)?

Skin permeation: QSPR model implemented from
Potts RO and Guy RH. 1992 Pharm. Res.

-5.92 cm/s

Druglikeness

Lipinski?

Lipinski (Pfizer) filter: implemented from
Lipinski CA. et al. 2001 Adv. Drug Deliv. Rev.
MW ≤ 500
MLOGP ≤ 4.15
N or O ≤ 10
NH or OH ≤ 5

 0.0
Ghose?

Ghose filter: implemented from
Ghose AK. et al. 1999 J. Comb. Chem.
160 ≤ MW ≤ 480
-0.4 ≤ WLOGP ≤ 5.6
40 ≤ MR ≤ 130
20 ≤ atoms ≤ 70

 None
Veber?

Veber (GSK) filter: implemented from
Veber DF. et al. 2002 J. Med. Chem.
Rotatable bonds ≤ 10
TPSA ≤ 140

 0.0
Egan?

Egan (Pharmacia) filter: implemented from
Egan WJ. et al. 2000 J. Med. Chem.
WLOGP ≤ 5.88
TPSA ≤ 131.6

 0.0
Muegge?

Muegge (Bayer) filter: implemented from
Muegge I. et al. 2001 J. Med. Chem.
200 ≤ MW ≤ 600
-2 ≤ XLOGP ≤ 5
TPSA ≤ 150
Num. rings ≤ 7
Num. carbon > 4
Num. heteroatoms > 1
Num. rotatable bonds ≤ 15
H-bond acc. ≤ 10
H-bond don. ≤ 5

 2.0
Bioavailability Score?

Abbott Bioavailability Score: Probability of F > 10% in rat
implemented from
Martin YC. 2005 J. Med. Chem.

0.55

Medicinal Chemistry

PAINS?

Pan Assay Interference Structures: implemented from
Baell JB. & Holloway GA. 2010 J. Med. Chem.

0.0 alert
Brenk?

Structural Alert: implemented from
Brenk R. et al. 2008 ChemMedChem

0.0 alert: heavy_metal
Leadlikeness?

Leadlikeness: implemented from
Teague SJ. 1999 Angew. Chem. Int. Ed.
250 ≤ MW ≤ 350
XLOGP ≤ 3.5
Num. rotatable bonds ≤ 7

 No; 1 violation:MW<1.0
Synthetic accessibility?

Synthetic accessibility score: from 1 (very easy) to 10 (very difficult)
based on 1024 fragmental contributions (FP2) modulated by size and complexity penaties,
trained on 12'782'590 molecules and tested on 40 external molecules (r2 = 0.94)

 1.0

Application In Synthesis of [ 403-42-9 ]

* All experimental methods are cited from the reference, please refer to the original source for details. We do not guarantee the accuracy of the content in the reference.

  • Downstream synthetic route of [ 403-42-9 ]

[ 403-42-9 ] Synthesis Path-Downstream   1~29

  • 1
  • [ 403-42-9 ]
  • [ 448-60-2 ]
YieldReaction ConditionsOperation in experiment
95% With para-dodecylbenzenesulfonic acid; In neat (no solvent); at 130℃; for 4.0h;Green chemistry; General procedure: A mixture of acetophenone (3 mmol) and DBSA (0.6 mmol) was heated at 130 C in a preheated oil bath for 3-8 hours. After completion of the reaction as indicated by thin layer chromatography (TLC), the reaction mixture was cooled to room temperature and diluted with equal volumes of saturated solution of NaHCO3 and brine (5 mL + 5 mL). The resulting solution was extracted with ethyl acetate (10 mL × 3) and the organic layers were combined, dried over anhydrous Na2SO4 and evaporated under reduced pressure to dryness. The crude product obtained was purified by silica gel (60-120 mesh size) column chromatography using 1-2% ethyl acetate in heptane as the eluent to afford the desired products in pure form.
92% With ethylenediamine; trifluoroacetic acid; In nitromethane; for 36.0h;Reflux; General procedure: To a solution of aryl methyl ketone (1, 1.5mmol) in dry nitromethane (1.5mL) was added trifluoroacetic acid (0.045 mL, 0.6mmol) and ethylenediamine (0.020 mL, 0.3mmol). The mixture was stirred at reflux and detected by TLC. After completion of the reaction, the reaction mixture was cooled to room temperature, quenched with saturated NH4Cl, extracted with Ethyl acetate. Combined organic layers were washed with brine, dried over Na2SO4, and concentrated. The residue was purified by silica gel column chromatography to give product 2.
83% With sulfated tungstate; In neat (no solvent); at 130℃; for 10.0h; General procedure: In round bottom flask equipped with condenser a mixture of aryl alkyl ketones (3mmol) and sulfated tungstate (20 wt. %) were stirred at 130 C, the progress of the reaction was monitored by TLC. After disapperance of the aryl alkyl ketones and the reaction was continued for additional time of 2 h. The reaction mixture was cooled, diluted with 30 mL of ethyl acetate and filtered to recover the catalyst. The filtrate was washed with 10 mL of water, dried over sodium sulfate and concentrated under reduced pressure. The residue was purified by column chromatography on silica gel ( 60-120) with (PE:EA=9:1) as eluent to get pure 1,3,5-arylenzenes.
65% With iodine; 1,2-diamino-benzene; In chlorobenzene; at 120℃; for 12.0h;Sealed tube; General procedure: Acetophenone 1 (1mmol), 2-amino aniline 2a (108mg, 1mmol), I2 (13mg, 5mol%), PhCl (3 mL) were added to a reaction tube. The reaction mixture was stirred in a sealed tube at 120 C for 12 h. The reaction was monitored by TLC. Once the reaction was completed, the reaction mixture was treated with H2O (15.0 mL) and EtOAc (8.0 mL). The organic phase was then separated, and the aqueous phase was extracted with EtOAc (3 x 8 mL). The combined organic phase was dried over Na2SO4, then the solvent was removed under a reduced pressure and the remaining residue was purified by column chromatography.

  • 2
  • [ 403-42-9 ]
  • [ 95-92-1 ]
  • [ 31686-94-9 ]
YieldReaction ConditionsOperation in experiment
96% With ethanol; sodium; at 10℃; Synthesis of ethyl 4-(4-fluorophenyl)-2,4-dioxobutanoate:In a 2L round bottom flask equipped with a reflux condenser and a CaCl2 drying tube metallic sodium (49.9 g, 2.17 mol, 3.0 equiv.) was dissolved in ethanol (1.0 L) carefully. The resulting sodium ethylate solution was cooled to about 10 C then the mixture of l -(4-fluorophenyl)ethan-l-one (100.0 g, 0.72 mol) and diethyl oxalate (2) (295 mL, 2.17 mol, 3.0 equiv.) was poured slowly into it. The reaction mixture was stirred for about 15 minutes, and then was allowed to stand in a refrigerator overnight. The reaction mixture was poured into a mixture of cone. HC1 solution (300 mL) and ice (c.a. 1 kg). The resulting precipitate was filtered off and washed with plenty of water, finally dried in a vacuum desiccator over P2O5/KOH. Yield: 165.5 g (3) (96%) as a light yellow .powder.
81% With sodium ethanolate; In ethanol; at 0 - 20℃; for 5h; sodium ethoxide (20 mL, 2.00 eq.) was added to a solution of 1-(4-fluorophenyl)ethan-1-one (5 g, 36.20 mmol, 1.00 eq.) and diethyl oxalate (5.29 g, 36.20 mmol, 1.00 eq.) in ethanol (50 mL) at 0C. The resulting solution was stirred for 5 hours at room temperature, diluted with 500 mL of water and thesolids were collected by filtration. This resulted in 7 g (8 1%) of ethyl 4-(4-fluorophenyl)-2,4- dioxobutanoate as a yellow solid.
81% With sodium ethanolate; In ethanol; at 0 - 20℃; for 5h; sodium ethoxide (20 mL, 2.00 eq.) was added to a solution of l-(4-fluorophenyl)ethan-l-one (5 g, 36.20 mmol, 1.00 eq.) and diethyl oxalate (5.29 g, 36.20 mmol, 1.00 eq.) in ethanol (50 mL) at 0C. The resulting solution was stirred for 5 hours at room temperature, diluted with 500 mL of water and the solids were collected by filtration. This resulted in 7 g (81%) of ethyl 4-(4-fluorophenyl)-2,4- dioxobutanoate as a yellow solid.
70% To a solution of sodium ethoxide (351 mL, 21% in ethanol, 1629 mmol) was added 1-(4-fluorophenyl) ethanone (150 g, 1086 mmol) in ethanol (100 mL) at 0 C. under a nitrogen atmosphere and the resulting reaction mixture was stirred at RT for 10 min Diethyl oxalate (156 mL, 1140 mmol) in ethanol (100 mL) was added and reaction was allowed to stir at RT for 12 h. Reaction mixture was cooled to 0 C. and acidified with 1.5 N HCl and the solid was filtered and the filtrate was diluted with water and extracted with DCM (3*750 mL). The combined organic layer was washed with brine, dried over Na2SO4, filtered and concentrated to afford Intermediate 1A (180 g, 70%) which was taken to next step without further purification. MS(ES): m/z=237 [M-H]+; 1H NMR (300 MHz, CDCl3) delta ppm 15.2 (bs, 1H), 8.00-8.09 (m, 2H), 7.15-7.25 (m, 2H), 7.05 (s, 1H), 4.42 (q, J=7.15 Hz, 2H), 1.43 (t, J=7.15 Hz, 3H).
70% To a solution of sodium ethoxide (351 mL, 21% in ethanol, 1629 mmol) was added l-(4-fluorophenyl) ethanone (150 g, 1086 mmol) in ethanol (100 mL) at 0 C under a nitrogen atmosphere and stirred at RT for 10 min. Diethyl oxalate (156 mL, 1140 mmol) in ethanol (100 mL) was added and reaction was allowed to stir at RT for 12 h. The reaction mixture was cooled to 0 C and acidified with 1.5 N HCl and the solid was filtered and the filtrate was diluted with water and extracted with DCM (3 x 750 mL). The combined organic layer was washed with brine, dried over Na2S04, filtered and concentrated to afford Intermediate 1A (180 g, 70%), which was taken to next step without further purification. MS(ES): m/z = 237 [M-H]+; 1H NMR (300 MHz, CDC13) delta ppm 15.2 (bs, 1H), 8.00 - 8.09 (m, 2H), 7.15 - 7.25 (m, 2H), 7.05 (s, 1H), 4.42 (q, J = 7.15 Hz, 2H), 1.43 (t, J= 7.15 Hz, 3H)
54% To a solution of diisopropyl amine (6.2mL, 44mmol) in THF (44mL) at 0C was added n-BuLi (16.2mL, 40.5mmol). The cloudy yellow solution was stirred at 0C for 30 min., then cooled to -78C. 4?-fluoroacetophenone (3.2mL, 26 mmol) was added slowly along the sides of the flask and was stirred for 15 min. Diethyl oxalate (7.9mL, 58 mmol) was added and the reaction stirred at -78C for 1 hour. The mixture was warmed to room temperature and stirred for 20 min and the reaction was quenched by the addition of 1M HCl. The organic solvent was removed by rotary evaporation. The aqueous phase was extracted with EtOAc (3× 75mL) and the combined organic layers were washed with 1M HCl (25mL), saturated aqueuos NaHCO3 (25mL), and brine (25mL). The organic phase was dried over Na2SO4, filtered, and concentrated. The crude material was purified by flash column chromatography and recrystallized from EtOH to obtain 2b (3.38 g, 54% yield) as a yellow solid. 1HNMR (500 MHz, CDCl3) delta 15.83 - 15.03 (m, 1H), 8.42 - 8.09 (m, 2H), 7.50 (s, 1H), 7.42 (t, J= 8.5Hz, 2H), 4.64 (q, J= 7.1Hz, 2H), 1.65(t, J= 7.2Hz, 3H). 13C NMR (125 MHz, CDCl3) delta 189.86, 169.33, 166.36 (d, J= 256.5Hz), 162.27, 131.50 (d, J= 2.5Hz), 130.72 (d,J= 9.5Hz) , 116.3 (d, J= 22.0Hz) , 97.96, 62.83, 14.25.
54% To a solution of diisopropyl amine (6.2 mL, 44 mmol) in THF (44 mL) at 0 C was added n-BuLi (16.2 mL, 40.5 mmol). The cloudy yellow solution was stirred at 0 C for 30 min., then cooled to -78 C. 4'-fluoroacetophenone (3.2 mL, 26 mmol) was added slowly along the sides of the flask and was stirred for 15 min. Diethyl oxalate (7.9 mL, 58 mmol) was added and the reaction stirred at -78 C for 1 hour. The mixture was warmed to room temperature and stirred for 20 min and the reaction was quenched by the addition of 1M HC1. The organic solvent was removed by rotary evaporation. The aqueous phase was extracted with EtOAc (3 x 75 mL) and the combined organic layers were washed with 1M HC1 (25 mL), saturated aqueuos NaHC03 (25 mL), and brine (25 mL). The organic phase was dried over Na2S04, filtered, and concentrated. The crude material was purified by flash column chromatography and recrystallized from EtOH to obtain 2b (3.38 g, 54 % yield) as a yellow solid. NMR (500 MHz, CDCl3) d 15.83 - 15.03 (m, 1H), 8.42 - 8.09 (m, 2H), 7.50 (s, 1H), 7.42 (t, J = 8.5 Hz, 2H), 4.64 (q, J = 7.1 Hz, 2H), 1.65 (t, J = 7.2 Hz, 3H). 13C NMR (125 MHz, CDCl3) d 189.86, 169.33, 166.36 (d, J = 256.5 Hz), 162.27, 131.50 (d, J = 2.5 Hz), 130.72 (d, J = 9.5 Hz)*, 116.3 (d, J = 22.0 Hz)*, 97.96, 62.83, 14.25.
Example 54 Ethyl 4-(4-fluorophenyl)-2,4-dioxobutanoate To a solution of sodium metal (1.03 g, 45.0 mmol) in ethanol (100 mL) were slowly added drops of 1-(4-fluorophenyl)ethanone (4.50 mL, 36.9 mmol) at 0 C. The solution was stirred for 30 min, and then slowly added drops of diethyl oxalate (5.50 mL, 40.5 mmol) at the same temperature. Following stirring overnight at room temperature, the progression of the reaction was monitored by TLC (Hexane:EtOAc=4:1). When the reaction was completed, the reaction mixture was concentrated in vacuo. To the concentrate, 6M HCl was added dropwise at 0 C., followed by extraction with dichloromethane and water. The organic layer thus formed was dried over anhydrous magnesium sulfate, filtered, and concentrated to afford the title compound without further purification (9.07 g, quant., yellow solid). 1H NMR (300 MHz, CDCl3) delta 8.09-8.04 (m, 2H), 7.24-7.20 (m, 2H), 7.07 (s, 1H), 4.44 (q, J=7.2 Hz, 2H), 1.45 (t, J=7.2 Hz, 3H)
To a stirred solution of NaH (60%) (15.0 g, 361mmol), in toluene (400mL) at 0 C, was added 4-fluoro acetophenone (25.0 g, 181mmol) drop wise at 0 C. The reaction mixture was then stirred at 0 C for 30 minutes. Diethyl oxalate (37mL, 271mmol) was added drop wise at 0 C. The reaction mixture was stirred at 25 C for 2h. The reaction mixture was diluted with water (lOOOmL) and extracted in ethyl acetate (250mL x 3). The organic layer was washed with brine (250mL), dried over anhydrous sodium sulphate and distilled off to obtain crude ethyl 4-(4-fluorophenyl)-2,4- dioxobutanoate (44.0 g) as a liquid. This was carry forward to next step without further purification. (238.96 [M+H]).
With sodium ethanolate; In ethanol; at 70℃; for 5h; General procedure: 0.1 mol (1 eq) of substituted acetophenone and 0.2 mol (29.2 g, 2 eq) of diethyl oxalate were weighed into a 250 ml three-Add 100ml absolute absolute ethanol,Slowly drop the newly prepared ethanol solution of sodium ethoxide,Plus,The temperature was raised to 70 C for 5 hours,TLC detection,No raw materials to replace acetophenone,Reaction finished,The system is reddish brown.Stop heating,The solvent was distilled off under reduced pressure,Dark red brown sticky material,With about 100 ml of water transferred to 200 ml of ice water,With concentrated hydrochloric acid 8ml adjusted to pH 1,Stirring for 30min, filtering,The filter cake was washed with ice ethanol.; The substituted acetophenones are p-fluoroacetophenone, p-chloroacetophenone, p-bromoacetophenone, p-methylacetophenone and p-trifluoro(2a-2e) are ethyl 4- (4-fluorophenyl) -2,4-dioxobutyrate, 4- (4- (4-fluorophenyl) Chlorophenyl) -2,4-dioxobutyrate, ethyl 4- (4-bromophenyl) -2,4-dioxobutyrate, 4- (4-methylphenyl) 2,4-dioxobutyrate, ethyl 4- (4-trifluoromethylphenyl) -2,4-dioxobutyrate, as follows:
With sodium hydride; In toluene; mineral oil; at 50℃; for 1.5h;Reflux; General procedure: To a stirred solution of appropriate methyl ketone (0.1 mol) in dry toluene (200 mL)was added a suspension of NaH in mineral oil (60%; 0.2 mol) in portions and the mixture was warmed to50 C. At this temperature a solution of diethyl oxalate (0.15 mol) in dry toluene (60 mL) was addeddropwise under stirring. The reaction mixture was refluxed for 1.5 h. Upon cooling to room temperatureacetic acid (0.25 mol) was added dropwise. The reaction mixture was washed with water (200 mL), organicphase was dried over MgSO4 and evaporated to dryness. The obtained crude diketone was dissolved inethanol (250 mL), hydrazine dihydrochloride (0.11 mol) was added and the mixture was refluxed for 3 h.After evaporation of solvent the residue was treated with water (200 mL) and kept under ice-cooling for 1 h.Crystals were filtered off and dried in air to afford the corresponding pyrazole. In some cases thus obtainedsubstance was purified by recrystallization from aqueous ethanol.
Sodium metal (60%, 15.06 g, 376 mmol) is added to dry ethanol (300 ml_), then 1-(4-fluorophenyl)- ethanone (40.0 g, 289 mmol) in dry THF is added at 0 C and stirred for 10 min. at this temperature. Diethyl oxalate (50.78 g, 347 mmol) is added and stirred for 16 h at ambient temperature. 2 N HCI is added. The formed solid is collected by filtration and dried.
With potassium tert-butylate; In N,N-dimethyl-formamide; at 0 - 45℃; for 1.75h; In a three-necked flask acetophenone (5g, 41.61 mmol) anddiethyl oxalate (6.76 mL, 50 mmol) were dissolved in anhydrousDMF 65 mL at 0 C and t-BuOK (2g, 83.25 mmol) was slowly added,the mixture was stirred at 0 C for 15 min and 30 min more at roomtemperature before heating at 45 C for 1h. Reaction was pouredinto water-acetic acid and product extracted with ethyl acetate.Organic layers were combined, washed with water and brine, driedover magnesium sulphate, filtered and concentrated to yield thetitle compound. MS (ESI) m/z (%): 237.2 [M H]

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  • 3
  • [ 391-12-8 ]
  • [ 403-42-9 ]
  • [ 18060-39-4 ]
  • 4
  • [ 50-00-0 ]
  • [ 403-42-9 ]
  • [ 51304-61-1 ]
  • N-<1-(4-fluorophenyl)propionyl>-4-(4-chlorophenyl)-1,2,3,6-tetrahydropyridine hydrochloride [ No CAS ]
  • 5
  • [ 403-42-9 ]
  • [ 100-10-7 ]
  • [ 28081-19-8 ]
YieldReaction ConditionsOperation in experiment
70% With sodium hydroxide; In ethanol; water; at 20℃; General procedure: A solution of benzaldehyde (12 g, 11.7 ml, 0.1 mol) in ethanol was mixed with acetophenone (10.60 g, 10.2 ml, 0.1 mol), and an aqueous solution of sodium hydroxide (10 %) was added to it till no turbidity occurs. The reaction mixture was stirred for 20 h and kept overnight at room temperature. The mixture was poured into crushed ice and acidified with dilute hydrochloric acid. The crude product so obtained was filtered and recrystallized from methanol and dried at room temperature. The completion of the reaction was monitored by running TLC (Singh et al., 2010).
28% With sodium hydroxide; In ethanol; at 20℃; General procedure: Into a solution of NaOH (1.5 eq.) in ethanol (10 mL) was added appropriate acetophenone (1 eq.) and a solution of substituted aldehyde (1 eq.) in ethanol. The reaction mixture was stirred at room temperature until the conversion was complete (monitored by TLC), when the solids were formed and precipitated. The solvent was removed under vacuum and the resulting crude product was recrystallized from suitable solvent to give pure compound.
With potassium hydroxide; In ethanol; water; at 20℃; for 6.0h; To a stirred solution of 4-dimethylaminobenzaldehyde (2.99g, 20mmol) and4'-fluoroacetophenone (2.76g, 20mmol) in EtOH (50mL), 20% wt KOH aqueous (20mL) was added and left toreact for 6h at room temperature. After completion of the reaction as indicated by TLC, water (30mL) was addedand the mixture was stirred for 1h. The pale yellow solid was obtained by filtration and desiccation.
  • 6
  • [ 1192-62-7 ]
  • [ 403-42-9 ]
  • [ 154258-82-9 ]
  • 7
  • [ 1779-49-3 ]
  • [ 116332-54-8 ]
  • [ 403-42-9 ]
  • 8
  • [ 1779-49-3 ]
  • [ 116332-54-8 ]
  • [ 403-42-9 ]
  • 1-deutero-4'-fluoroacetophenone [ No CAS ]
  • 9
  • [ 403-42-9 ]
  • [ 4637-24-5 ]
  • [ 154258-82-9 ]
YieldReaction ConditionsOperation in experiment
Production Example 1 3-(4-Fluerophenyl)-1H-pyrazole 25 g 4'-fluoroacetophenone and 24 g N,N-dimethylformamide dimethyl acetal were heated for 6 hours under reflux, concentrated and evaporated into dryness to give 34.3 g of a reddish brown solid.. The product was dissolved in 150 ML ethanol, and 9.9 ML hydrazine monohydrate was added thereto and heated at 70C for 2 hours.. The reaction solution was poured into water, extracted with ethyl acetate and dried over magnesium sulfate, and the solvent was evaporated.. The product was recrystallized from ethyl acetate and hexane to give 24.5 g pale yellow crystals.1H-NMR (CDCl3) delta: 6.57(d, J=2. 4Hz, 1H), 7.05-7.12(m, 2H), 7.60(d, J=2. 4Hz, 1H), 7.70-7.76(m, 2H)
  • 10
  • [ 400-93-1 ]
  • [ 403-42-9 ]
  • [ 2105-96-6 ]
YieldReaction ConditionsOperation in experiment
With peracetic acid; sulfuric acid; nitric acid; acetic acid; In water; Example 23 Preparation of 4-fluoro-3-nitrophenol (23) To 15 mL of concentrated sulfuric acid at 0° C. is added 6.9 g (0.05 mmol) of 4-fluoroacetophenone. To the resulting solution is rapidly added a mixture of 4 mL nitric acid and 6 mL concentrated sulfuric acid. The reaction mixture is stirred at 0-5° C. for 3 hours. The reaction mixture is then poured into ice water, and the resulting mixture is extracted with chloroform. The combined organic fractions are washed with water, dried over anhydrous sodium sulfate, filtered and concentrated under reduced pressure. The resulting residue is purified using column chromatography on silica gel, eluding with 20percent ethyl acetate/hexanes, yielding 6.0 g of 4-fluoro-3-nitroacetophenone (60percent yield). Concentrated sulfuric acid (200 mL) and acetic acid (120) mL are mixed at 0° C. To this solution is added 15 g (0.082 mol) of 4-fluoro-3-nitroacetophenone with stirring. To the cold reaction mixture is added 36 mL of 36percent peracetic acid. The reaction mixture is then stirred at room temperature for 4 hours. Water (500 mL) is added to the mixture, and the crude product is extracted into diethyl ether. The combined ether fractions are washed with water, dried over anhydrous sodium sulfate, filtered and concentrated under reduced pressure. The residue is purified using column chromatography on silica gel, eluding with 3percent methanol/chloroform, giving 3.2 g of Compound 23 (20percent yield). mp: 86-87° C. 1 H-NMR (CDCl3) 7.56 (dd, 1H); 7.29 (t, 1H), 7.12 (m, 1H); 5.36 (s, 1H). 19 F-NMR (d6 -DMSO) 147.60 (s). Anal. calc. for C6 H4 FNO3: C, 45.87; H, 2.57; N, 8.92. Found: C, 45.80; H. 2.51; N, 8.69.
  • 11
  • [ 403-42-9 ]
  • [ 456-00-8 ]
YieldReaction ConditionsOperation in experiment
With hydrogenchloride; hexamethylenetetramine; bromine; sodium carbonate; In methanol; diethyl ether; ethanol; chloroform; A. N-[2-(4-Fluorophenyl)-2-oxoethyl)-[[(2,4-dioxo-1-imidazolidinyl)-imino]methyl]formamide 4'-Fluoroacetophenone (122 ml, 138 g, 1.00 mole) was combined with diethyl ether (300 ml) and the solution was cooled to 5. Bromine (54.5 ml, 1.00 mole) was added dropwise to the stirred solution, keeping the temperature at 5, over a three hour interval. The solution was washed with water and a dilute solution of sodium carbonate. The ether layer was dried over sodium sulfate and the ether was evaporated under pressure. The remaining solid was dissolved in chloroform (200 ml) and combined with a solution of hexamethylenetetramine (140 g, 1.00 mole) in chloroform (1 liter). A precipitate formed upon addition and stirring was continued for three hours. The addition product was collected and was washed with carbon tetrachloride to give 338 g (95%). All of the addition product was combined with ethanol (720 ml) and concentrated hydrochloric acid (620 ml). The solution was stirred for 0.5 hour when a light yellow precipitate formed and stirring was continued for 20 hours. The solid was collected and the filtrate was evaporated under reduced pressure. The residue was combined with the collected solid, and the mixture was recrystallized from a solution of methanol (1300 ml) and conc. hydrochloric acid (1%) to give 69.6 g of 2-amino-4'-fluoroacetophenone hydrochloride.
  • 12
  • [ 403-42-9 ]
  • [ 51012-64-7 ]
  • [ 1014980-85-8 ]
  • 13
  • [ 403-42-9 ]
  • [ 16732-66-4 ]
  • [ 1176887-34-5 ]
  • 14
  • [ 54589-54-7 ]
  • [ 403-42-9 ]
  • [ 1265614-73-0 ]
  • 15
  • [ 403-42-9 ]
  • [ 110677-45-7 ]
  • [ 1367364-39-3 ]
YieldReaction ConditionsOperation in experiment
54% With sodium hydroxide; In ethanol; at 20℃; for 12h; The 4-(9-(9H-carbazolyl)) benzaldehyde (217 mg, 0 . 8mmol), 1-(4-fluoro-phenyl) ethanone (0.8mmol), NaOH (40 mg, 1mmol) in 25 ml single-port the bottle, by adding 10 ml anhydrous ethanol, stirring the mixture at room temperature for 12h, TLC monitoring, most of the point of disappearance of the raw materials, to stop the reaction. Evaporate the solvent, the remaining solid washing with water to neutral, drying, column chromatography separation, a to get the yellow solid, yield 54%.
  • 16
  • [ 6374-91-0 ]
  • [ 403-42-9 ]
  • C16H10Br2FNO3 [ No CAS ]
YieldReaction ConditionsOperation in experiment
With sodium hydroxide; In ethanol; water; at 20℃; for 2h; General procedure: An aqueous solution of sodium hydroxide (5%, 10mL) was added slowly to the stirring solution of isatin (1mmol) and appropriate aryl acetophenone (1mmol) in ethanol (20mL) in 100mL conical flask. The stirring was continued for 2h and the completion of reaction was monitored by TLC. The reaction on completion was poured onto ice, solid obtained after filtration was crystallized from ethanol. The physical data for the characteristic compound is shown below:
  • 17
  • [ 92-55-7 ]
  • [ 403-42-9 ]
  • (3'R,4'R)-4'-(4-fluorobenzoyl)-1'-methyl-3'-(5-nitro-2-furyl)spiro[indene-2,2'-pyrrolidine]-1,3-dione [ No CAS ]
  • 18
  • [ 92-55-7 ]
  • [ 403-42-9 ]
  • [ 63421-80-7 ]
  • 19
  • [ 39974-94-2 ]
  • [ 403-42-9 ]
  • C19H16FNO2 [ No CAS ]
YieldReaction ConditionsOperation in experiment
With potassium hydroxide; In ethanol; at 20℃; for 24h; General procedure: The relevant N-methyl intermediate (3a-c, 2 mmol), acetophenonederivate (2 mmol) and potassium hydroxide (6 mmol) wasdissolved in ethanol (20 mL) and stirred for 24 h. Then the reactionmixture was filtered and washed with water and cold ethanol. Thecrude product was purified by recrystallization from ethanol anddichloromethane to give pure chalcone (4a-q) with yields of34.2-93.1%.
  • 20
  • [ 10102-94-0 ]
  • [ 403-42-9 ]
  • C18H13BrFNO [ No CAS ]
YieldReaction ConditionsOperation in experiment
With potassium hydroxide; In ethanol; at 20℃; for 24h; General procedure: The relevant N-methyl intermediate (3a-c, 2 mmol), acetophenonederivate (2 mmol) and potassium hydroxide (6 mmol) wasdissolved in ethanol (20 mL) and stirred for 24 h. Then the reactionmixture was filtered and washed with water and cold ethanol. Thecrude product was purified by recrystallization from ethanol anddichloromethane to give pure chalcone (4a-q) with yields of34.2-93.1%.
  • 21
  • [ 55984-93-5 ]
  • [ 403-42-9 ]
  • C16H14FNO [ No CAS ]
  • 22
  • [ 403-42-9 ]
  • [ 4494-26-2 ]
  • 5-((E)-3-(4-fluorophenyl)-3-oxopropen-1-yl)-2'-deoxyuridine [ No CAS ]
YieldReaction ConditionsOperation in experiment
50% With sodium hydroxide; In ethanol; water; at 0℃; <strong>[4494-26-2]5-formyl-2'-deoxyuridine</strong> (0.256 g, 1 mmol) And p-fluoroacetophenone (0.138 g, 1 mmol) Was added to an ethanol / water solution (5 mL) having a volume ratio of 1: 1, Then sodium hydroxide (0.060 g, 1.5 mmol) was added, The reaction was stirred at 0 C, TLC is tracked to the end of the reaction. After removing the solvent under reduced pressure, The residue was purified by column chromatography to give the yellow solid product d (0.188 g) Yield 50%.
  • 23
  • [ 108-86-1 ]
  • [ 403-42-9 ]
  • [ 347-84-2 ]
YieldReaction ConditionsOperation in experiment
90% With C16H14N6O4Pd; potassium tert-butylate; In acetonitrile; at 82℃; for 2h;Schlenk technique; Reflux; General procedure: An oven-dried, resealable Schlenk tube containing a stirbar was charged with aryl halide (1.0 mmol), ketone(1.1 mmol), potassium tert-butoxide (1.5 mmol), and1.0 mol % catalyst. Acetonitrile (10 mL) was sequentiallyadded and the tube was backfilled with nitrogen, and themixture was stirred in an oil bath at reflux temperature forthe time specified. After the reaction was completed, thesolvent was removed on a rotary evaporator and the mixturewas purified by chromatography on silica gel. The pure product was obtained, and the yield was calculated basedon ArX.
  • 25
  • [ 28785-06-0 ]
  • [ 403-42-9 ]
  • C18H17FO [ No CAS ]
YieldReaction ConditionsOperation in experiment
With sodium hydroxide; In ethanol; at 20℃; General procedure: p-Fluoro acetophenone 6 (0.01 mol) and benzaldehyde Ia(0.01 mol) were dissolved in 15 mL ethanol. NaOH solution(0.02 mol) in ethanol was added slowly and the mixture wasstirred at 20 °C for 2 h until the entire mixture becomes verythick. The progress of the reaction was monitored by TLC(toluene: acetone, 80:20). Then the reaction mixture waspoured slowly onto 400 mL of water with stirring and keptin refrigerator for 24 h. The precipitate obtained was filtered,washed, and recrystallized from ethanol. The othercompounds IIb?j were prepared by the same method usingsubstituted benzaldehydes Ib?j.
  • 26
  • [ 103854-64-4 ]
  • [ 403-42-9 ]
  • C19H14FNO2 [ No CAS ]
  • 27
  • [ 108-86-1 ]
  • [ 403-42-9 ]
  • [ 347-84-2 ]
  • [ 2193-29-5 ]
YieldReaction ConditionsOperation in experiment
70%Chromat.; 6%Chromat. With potassium tert-butylate; In acetonitrile; at 81℃; for 2h;Inert atmosphere; Schlenk technique; General procedure: The catalytic experiments were carried out using potassium tertbutoxide(1.5 mmol) as a base, functionalized silica materials (approx.Pd content 1.0 mol%) as catalyst, and ketone (1.0 mmol), and aryl halide(1.2 mmol) as reagents in acetonitrile (10 mL) at reflux temperature.After cooling the reaction mixture, the reaction vessel was centrifugedto settle the silica and the catalyst was separated from theliquid product by decanting the supernatant carefully and then filtration.The filtrate was analyzed by gas chromatography to determine theyield of the product. The recovered catalyst was washed twice withCH2Cl2 and dried in vacuo. It was then used for the next run.
  • 28
  • [ 403-42-9 ]
  • [ 1671-88-1 ]
  • 6-(4-fluorophenyl)-3-(pyridin-2-yl)-7H-pyrido[2,1-d][1,2,4]triazolo[4,3-b][1,2,5]triazepin-8-ium iodide [ No CAS ]
  • 29
  • [ 403-42-9 ]
  • [ 870704-22-6 ]
 

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