* 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.
57aTo a solution of ethyl 3-bromopropanoate (120 g, 663 mmol) in acetone (500 mE) was added Nal (150 g, 1.00 mol). The resulting solution was heated at reflux for 5 h and allowed to cool to rt. Et20 (500 mE) was added. The solids formed were removed by filtration. The filtrate was concentrated in vacuo. The resulting residue was treated with Et20 (150 mE) and filtered. The filtrate was washed with saturated NaHCO3 solution (2x50 mE). The organic layer was dried over Na2504, filtered and concentrated under reduced pressure to obtain compound 57a as a yellow oil. Mass Spectrum (GCMS, ESI pos.): Calcd. for C5H9102: 228.0 (M). Found:228.0.
With sodium hydrogencarbonate; triethylamine; In hexane; ethyl acetate;
EXAMPLE 1 2'-(N-2-Carbethoxyethylamino)-3',4'-dimethoxyacetophenone Triethylamine (19.4 g, 192 mM) was added to a mixture of <strong>[49701-79-3]2'-amino-3',4'-dimethoxyacetophenone</strong> (25 g, 128 mM) and ethyl 3-bromopropionate (139 g, 770 mM), in a 250 mL flask (equipped with a large stirring bar, reflux condenser and nitrogen inlet). The pale solid which formed was stirred at 135 C. for 5 hours. The brown homogeneous oil which formed was then cooled to 10 C. and 200 mL of 2% NaHCO3 was added. The solution was then extracted with CHCl3 (3*100 mL), the organic layer washed with H2 O (100 mL) and dried over MgSO4. Following filtration, the CHCl3 and most of the bromopropionate were removed under reduced pressure. The oily residue was charged onto a 10*75 cm, SilicAR CC-7 column (800 g, hexane packed) and eluted with 5 to 20% ethylacetate/hexane, collecting 1 L fractions. Evaporation of fractions 7-9 gave purified 2'-(N-2-carbethoxyethylamino)-3',4'-dimethoxyacetophenone as a yellow oil (5.86 g, 15%); UV (EtOH) nm: 244 (epsilon29110), 284 (epsilon11480); MS (Probe) 295 (M+).
15%
With sodium hydrogencarbonate; triethylamine; In hexane; ethyl acetate;
EXAMPLE 1 2'-(N-2-Carbethoxyethylamino)-3',4'-dimethoxyacetophenone Triethylamine (19.4 g, 192 mM) was added to a mixture of <strong>[49701-79-3]2'-amino-3',4'-dimethoxyacetophenone</strong> (25 g, 128 mM) and ethyl 3-bromopropionate (139 g, 770 mM), in a 250 mL flask (equipped with a large stirring bar, reflux condenser and nitrogen inlet). The pale solid which formed was stirred at 135 C. for 5 hours. The brown homogeneous oil which formed was then cooled to 10 C. and 200 mL of 2% NaHCO3 was added. The solution was then extracted with CHCl3 (3*100 mL), the organic layer washed with H2 O (100 mL) and dried over MgSO4. Following filtration, the CHCl3 and most of the bromopropionate were removed under reduced pressure. The oily residue was charged onto a 10*75 cm, SilicAR CC-7 column (800 g, hexane packed) and eluted with 5 to 20% ethyl acetate/hexane, collecting 1 L fractions. Evaporation of fractions 7-9 gave purified 2'-(N-2-carbethoxyethylamino)-3',4'-dimethoxyacetophenone as a yellow oil (5.86 g, 15%); UV (EtOH) nm: 244 (epsilon29110), 284 (epsilon11480); MS (Probe) 295 (M+).
2-[1-(2-ethoxycarbonyl-ethyl)-7-(3-morpholin-4-yl-propylamino)-2,4-dioxo-1,4-dihydro-2<i>H</i>-pyrimido[4,5-<i>d</i>]pyrimidin-3-yl]-3-phenyl-propionic acid ethyl ester[ No CAS ]
With hydrogenchloride; methylmagnesium bromide; In tetrahydrofuran;
EXAMPLE 22 Preparation of 4-bromo-2-methyl-2-butanol To a solution of 6.25 g (34.5 mmol) of ethyl 3-bromopropionate in 28 ml of dry tetrahydrofuran at -20 C. was added dropwise 28.8 ml (80.6 mmol) of 2.8M methylmagnesium bromide in ether. The mixture was stirred at room temperature for 2 hours and 50 minutes then quenched by addition of 15 ml of saturated aqueous ammonium chloride. After addition of 42 ml of 1N aqueous HCl, the organic phase was separated and the aqueous phase extracted with ether. The combined organic extracts were washed with saturated brine, dried (Na2 SO4) and evaporated to dryness. The residue was chromatographed on silica gel (40-63μ) using 30% ethyl acetate-hexane to give 2.57 g (45%) of 4-bromo-2-methyl-2-butanol as an oil: IR (CHCl3) 3605 cm-1; 1 H NMR (CDCl3) δ1.27 (s, 6 H), 1.33 (s, 1 H), 2.11 (m, 2 H), 3.51 (m, 2 H); MS m/e 151 (M+ --CH3).
4-Bromo-2-methylbutan-2-ol Methylmagnesium bromide (3M in diethyl ether, 46 ml) was added to a solution of ethyl 3-bromopropionate (10 g) in diethyl ether (100 ml) at room temperature under argon. During this, the mixture was kept at above 20 C. and below 35 C. After 2 hours, the mixture was poured into a saturated ammonium chloride solution. This was followed by extraction with diethyl ether, drying with sodium sulfate, filtration and concentration. This resulted in the desired product.
This compound was synthesized using the procedure described in example 2, step B, from 5-iodo-l,3-dimethyl-2-nitrobenzene (see example 2) and ethyl 3-bromopropanoate
General procedure: A mixture of <strong>[271-73-8]1H-<strong>[271-73-8]pyrazolo[3,4-b]pyridine</strong></strong> 2 (1 eq.) and K2CO3 (10 eq.) in DMF was stirred at 80 °C. After 30 min, excess Br(CH2)nCO2Et was added and the reaction mixture was stirred for 1 h at 80 °C. Upon cooling, the mixture was acidified with 10percent aqueous HCl solution and the aqueous layer was extracted with EtOAc. The combined organic extracts were washed with brine and dried over anhydrous MgSO4. After filtration, the solvent was removed in vacuum and the resulting oil was purified by column chromatography (1:1 ethyl ether:petroleum ether).
ethyl 4-(4-bromo-2,6-difluorophenyl)-4-cyanobutanoate[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
96.5%
To a solution of <strong>[537033-52-6]2-(4-bromo-2,6-difluorophenyl)acetonitrile</strong> (10 g,43.1 mmol)in THF (150 mL) was added LDA (2 M in THF,24 mL,48 mmol) dropwise in 20 min at -65 , the reaction solution was stirred for 1 hour at this temperature, then to this was added ethyl 3-bromopropanoate (9.4 g,51.7 mmol)in THF (30 mL) dropwise in 10 min. The resulting solution was stirred for 30 min at -65 , and then allowed to warm to room temperature naturally. The reaction was quenched by the addition of sat. aq. NH 4Cl (50 mL) , and extracted with EtOAc (100 mL x 3) . The combined organic layers were washed with brine, dried over anhydrous Na 2SO 4. After filtration, the filtrate was concentrated under reduced pressure to afford the product (13.8 g, 96.5%) . [M+H] + = 332.0.
96.5%
To a solution of <strong>[537033-52-6]2-(4-bromo-2,6-difluorophenyl)acetonitrile</strong> (10 g,43.1 mmol)in THF (150 mL) was added LDA (2 M in THF,24 mL,48 mmol) dropwise in 20 min at -65 , the reaction solution was stirred for 1 hour at this temperature, then to this was added ethyl 3-bromopropanoate (9.4 g,51.7 mmol)in THF (30 mL) dropwise in 10 min. The resulting solution was stirred for 30 min at -65 , and then allowed to warm to room temperature naturally. The reaction was quenched by the addition of sat. aq. NH 4Cl (50 mL) , and extracted with EtOAc (100 mL x 3) . The combined organic layers were washed with brine, dried over anhydrous Na 2SO 4. After filtration, the filtrate was concentrated under reduced pressure to afford the product (13.8 g, 96.5%) . [M+H] + = 332.0.
With potassium carbonate; In acetone; for 12h;Reflux;
General procedure: 6-Substituephenyl-3( 2H )-pyridazinonederivative(1equiva-lent), ethyl 3-bromopropionate (18.1 g, 2 equivalent) and potassiumcarbonate (13.6 g, 2 equivalent) in 50 ml acetone were heated un-der reflux for 12 h. After that, it was poured into ice water and theprecipitate was filtered off, dried and recrystallized from ethanol.
Chemistry
Pharmaceutical Intermediates
Inhibitors/Agonists
Material Science
For Research Only
120K+ Compounds
Competitive Price
1-2 Day Shipping
