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Synonyms: 5-Bromo-2-fluoro-benzaldehyde
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CAS No. : | 93777-26-5 |
Formula : | C7H4BrFO |
M.W : | 203.01 |
SMILES Code : | C1=C(C(=CC=C1Br)F)C=O |
Synonyms : |
5-Bromo-2-fluoro-benzaldehyde
|
MDL No. : | MFCD00070755 |
InChI Key : | MMFGGDVQLQQQRX-UHFFFAOYSA-N |
Pubchem ID : | 736327 |
GHS Pictogram: |
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Signal Word: | Warning |
Hazard Statements: | H315-H319-H335 |
Precautionary Statements: | P261-P305+P351+P338 |
* 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.
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
75% | With triethylamine; In dimethyl sulfoxide; at 95℃; for 2h; | (a) Ethyl thioglycolate, Et3N, DMSO, 95 C., 2 h [0304] The substance was obtained according to the general procedure, yielding the title compound as a off-white crystals (75%). [0305] 1H-NMR (400 MHz, DMSO-d6); δ (ppm): 1.33 (t, 3H), 4.36 (dd, 2H), 7.63 (d, 1H), 8.04 (d, 1H), 7.13 (s, 1H), 7.25 (s, 1H) |
With potassium carbonate; In N,N-dimethyl-formamide; at 20 - 80℃; for 2.5h; | 5-Bromo-2-fluorobenzaldehyde (25 g) and potassium carbonate (34 g) were suspended in N,N-dimethylformamide (125 ml), and ethyl thioglycolate (14.2 ml) was added dropwise. After being stirred for 30 minutes at room temperature, this was heated for 2 hours at 80C. It was then poured into ice-cooled aqueous citric acid solution and extracted with ethyl acetate, the organic layer was washed with water and sodium chloride solution and dried over magnesium sulfate, and the solvent was evaporated. The precipitated crystals were filtered out and washed with hexane to obtain ethyl 5-bromo-1-benzothiophen-2-carboxylate (29.2 g) as colorless crystals. 1H-NMR (300MHz, CDC13) 5 1.42 (3H, t, J = 7.2 Hz), 4.41 (2H, q, J = 7.2 Hz), 7.54 (1H, dd, J = 1.7, 8.7 Hz), 7.73 (1H, d, J = 8.7 Hz), 7.97 (1H, s), 8.01 (1H, d, J = 1.7 Hz) | |
With sodium carbonate; | Example 218 Synthesis of ethyl 5-bromobenzo[b]thiophene-2-carboxylate. To a solution of 5-bromo-2-fluorobenzaldehyde (2.03 g, 10 mmol) and ethyl 2-mercaptoacetate (1.2 g, 10 mmol) in EtOH (40 mL) was added Na2CO3 (1.27 g, 12 mmol). The reaction mixture was stirred at reflux for 14 h. Then the mixture was concentrated in vacuo. Water (20 mL) was added and the mixture was extracted with DCM (50 mL*3). The combined organic layers were concentrated to give the crude product, which was purified by silica gel chromatography (PE/EtOAc=1/1) to give the ethyl 5-bromobenzo[b]thiophene-2-carboxylate as a yellow solid (2.3 g, yield: 80%). ESI-MS [M+H]+: 284.7, 286.7. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
70% | With diethylamino-sulfur trifluoride; In dichloromethane;Heating / reflux; | 5-Bromo-2-fluorobenzaldehyde (2 g, 9.8 mmol) in CH2Cl2 (50 ml) was treated at 0C. with (diethylamino)sulfur trifluoride (2 ml, 14.8 mmol). The reaction mixture was refluxed overnight and then quenched with saturated solution of NaHCO3. The aqueous phase was extracted with ethyl acetate. The combined organic layers were washed with brine, dried over MgSO4, filtered and concentrated in vacuo. The residue was chromatographed over silica gel (hexane-ethyl acetate 99 : 01) to provide 4-bromo-2-difluoromethyl-1-fluoro-benzene (1.55 g, 70%) as a colorless oil, MS: m/e=226.0 (M+H+). |
61% | With diethylamino-sulfur trifluoride; In dichloromethane; at 20.0℃; for 18.0h;Inert atmosphere; | [143] To a solution of 5-bromo-2-fluoro-benzaldehyde (4.06 g, 20 mmol) in DCM (50 mL) was added DAST (diethylaminosulfur trifluoride) (4.03 g, 25 mmol) and the mixture was stirred at room temperature for 18 hours under nitrogen atmosphere. The reaction mixture was quenched into ice-water and extracted with DCM. The organic layer was dried and concentrated. Yield: 2.74 g (61 %) |
With diethylamino-sulfur trifluoride; In dichloromethane; at 20.0℃; for 1.0h; | Preparation 3:4-BROMO-2-(DIFLUOROMETHYL)-l-FLUOROBENZENE5-bromo-2-fluorobenzaldehyde (2.0 g, 9.85 mmol) and diethylaminosulfur trifluo?de (2.2 ml) was stirred at ambient temperature for 1 hour. Methylene chloride (100 ml) was added and the solution was cooled to 0 0C. Aqueous sodium bicarbonate (10%, 50 ml) was added slowly and the phases were separated. The organic phase was washed with water (50 ml), dried (MgSO4), filtered and evaporated to dryness to yield the crude product (1.79 g). MS m/z (rel. intensity, 70 eV) 226 (M+, 98), 224 (M+, bp), 207 (17), 145 (79), 125 (22). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With hydrogenchloride; iron(III) chloride; In water; N,N-dimethyl-formamide; | Step A 5-Cyano-2-fluorobenzaldehyde To a solution of 5-bromo-2-fluorobenzaldehyde (1.93 g, 9.51 mmol) in DMF (4 mL) was added copper(I) cyanide (0.98 g, 10.93 mmol). The mixture was heated to 190 ° C. and stirred for 5 h. The dark brown reaction mixture was poured into a solution containing ferric chloride (3.0 g), conc. HCl (0.93 mL) and water (6 mL) and warmed to 65 ° C. for 20 min. The mixture was partitioned between toluene (20 mL) and water (20 mL). The organic was washed with diluted HCl (25 mL), water (20 mL), 10percent sodium hydroxide (25 mL), dried over magnesium sulfate, and concentrated to provide a solid product: 1H NMR (CDCl3) delta 10.34 (m, 1H), 8.21 (m, 1H), 7.90 (m, 1H), 7.35 (m, 1H). | |
With hydrogenchloride; iron(III) chloride; In water; N,N-dimethyl-formamide; | Step A 5-Cyano-2-fluorobenzaldehyde To a solution of 5-bromo-2-fluorobenzaldehyde (1.93 g, 9.51 mmol) in DMF (4 mL) was added copper(I) cyanide (0.98 g, 10.93 mmol). The mixture was heated to 190° C. and stirred for 5 h. The dark brown reaction mixture was poured into a solution containing ferric chloride (3.0 g), conc. HCl (0.93 mL) and water (6 mL) and warmed to 65° C. for 20 min. The mixture was partitioned between toluene (20 mL) and water (20 mL). The organic was washed with diluted HCl (25 mL), water (20 mL), 10percent sodium hydroxide (25 mL), dried over magnesium sulfate, and concentrated to provide a solid product: 1H NMR (CDCl3) delta 10.34 (m, 1H), 8.21 (m, 1H), 7.90 (m, 1H), 7.35 (m, 1H). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
In N-methyl-acetamide; | PREPARATION 88(1) To a solution of 5-bromo-2-fluorobenzaldehyde (10 g) in dimethylformamide (60 mL) were added zinc cyanide (6.92 g) and tetrakis(triphenylphosphine)palladium(O) (2.28 g), and the mixture was stirred at 80° C. for 6 hours. The resulting mixture was diluted with ethyl acetate and washed successively with water and brine. The organic layer was dried over sodium sulfate and evaporated in vacuo. The residue was subjected to a silica gel column chromatography eluding with a mixture of hexane and ethyl acetate (3:1) to give 5-cyano-2-fluorobenzaldehyde (5.3 g) as a solid substance. NMR (DMSO-d6, delta): 7.35 (1H, t, J=9 Hz), 7.91 (1H, m), 8.22 (1H, dd, J=2, 7 Hz), 10.36 (1H, s); Mass m/z: 150 (M++1). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
70% | With diethylaminosulfur trifluoride; In dichloromethane; | 4-Bromo-2-difluoromethyl-1-fluoro-benzene 5-Bromo-2-fluorobenzaldehyde (2 g, 9.85 mmol) was dissolved in CH2Cl2 (50 ml). The reaction mixture was put under an argon atmosphere and cooled to 0 C. Diethylaminosulfur trifluoride (2.04 ml, 14.78 mmol) was added dropwise. The mixture was allowed to warm up to room temperature and stirred overnight. It was then quenched with a saturated aqueous NaHCO3 solution. The layers were separated and the aqueous one was extracted with CH2Cl2. The combined organic phases were dried with Na2SO4 and the solvent evaporated. The brown oil was chromatographed (silica, elution hexane/AcOEt) to afford the title compound (1.55 g, 70%) as a colorless oil. MS: m/e=226.0 (M+H+). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
86% | With hydrogenchloride; sodium carbonate; In hexane; water; dimethyl sulfoxide; | Example 1 Synthesis of 4-(4-bromo-2-formyl-N-methylanilino)-butyric acid To a suspension of 5-bromo-2-fluorobenzaldehyde (20.3 g) and <strong>[6976-17-6]4-methylaminobutyric acid hydrochloride</strong> (18.4 g) in DMSO/water(100 ml/100 ml) was slowly add sodium carbonate (25.4 g), followed by stirring at 105°C to 110°C for 3.5 hours. The mixture was cooled to 50°C to 60°C, atwhich temperature 6N hydrochloric acid was added dropwise to adjust the pH to 3. The mixture was extracted with ethyl acetate (200 ml + 100 ml), and the organic layer was washed with a saturated aqueous sodium chloride solution (40 ml * 2) and water (40ml). The organic layer was concentrated, and the concentrate was then dissolved in IPE (50 ml), to which n-hexane (50 ml) was added dropwise. The precipitates were filtered out and washed with IPE/n-hexane (16 ml/4 ml). The filter cake was dried under reduced pressure at room temperature for 4 hours to give 4-(4-bromo-2-formyl-N-methylanilino)butyric acid (25.9 g, 86percent yield) as yellow crystals. 1H-NMR (CDCl3, delta, 300 MHz): 1.95 (2H, tt, J = 6.5, 7.4 Hz), 2.38 (2H, t, J = 6.5 Hz), 2.88 (3H, s), 3.17 (2H, t, J = 7.4 Hz), 7.01 (1H, d, J = 8.7 Hz), 7.55 (1H, dd, J = 8.7, 2.5 Hz), 7.87 (1H, d, J = 2.5 Hz), 10.16 (1H, s). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
60% | In N,N-dimethyl-formamide;Reflux; | A mixture of 74 (1.82 g, 9 mmol) and copper (I) cyanide (1.4 g, 15.7 mmol) in DMF (14.0 mL) was stirred at reflux overnight. After completion, the reaction mixture was cooled to rt and poured into a solution of water (10 mL) and NH4OH (10 ml) followed by extraction with EtOAc (3 x 25 mL). The organic layer was sequentially washed with brine (2 x 15 mL), dried over anhydrous Na2S04, and concentrated in vacuo to give 757a (0.80 g, 60 percent). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
58.4% | With dicyclohexyl-(2',6'-dimethoxybiphenyl-2-yl)-phosphane; tris-(dibenzylideneacetone)dipalladium(0); sodium carbonate; In 1,2-dimethoxyethane; water; toluene; at 100 - 120℃; for 2.5h;Microwave irradiation; | 4-(Benzyloxy)-2,6-dimethylphenyl)boronic acid 12b (256 mg, 1 mmol), 2-fluoro-5-bromo-benzaldehyde (203 mg, 1 mmol), 2 M aqueous sodium carbonate solution (1 mL, 2 mmol), 2-dicyclohexylphosphino-2',6'-dimethoxybiphenyl (37 mg, 0.08 mmol) and tris(dibenzylideneacetone)dipalladium (18 mg, 0.02 mmol) were dissolved in 3 mL of the mixture solvent of ethylene glycol dimethyl ether and toluene (V/V = 1:2). The reaction mixture was heated at 100 C for 2 hours, and then at 120C for 0.5 hours under micarowave condition. The resulting mixture was added with 10 mL of water and extracted with ethyl acetate (10 mL*3). The combined organic extracts were washed with saturated sodium chloride solution (30 mL), dried with anhydrous magnesium sulphate and filtered. The filtrate was concentrated under reduced pressure. The residue was purified by silica gel column chromatography with elution system B to obtain the title compound 4'-(benzyloxy)-4-fluoro-2',6'-dimethylbiphenyl-3-carbaldehyde 18a (390 mg, yield 58.4%) as a colorless oil. MS m/z (ESI): 335.2 [M+1] |
58.4% | With dicyclohexyl-(2',6'-dimethoxybiphenyl-2-yl)-phosphane; tris-(dibenzylideneacetone)dipalladium(0); sodium carbonate; In 1,2-dimethoxyethane; water; toluene; at 100 - 150℃; for 2.5h;Microwave irradiation; Inert atmosphere; | (4-(Benzyloxy)-2,6-dimethylphenyl)boronic acid 12b (256 mg, 1 mmol), 2-fluoro-5-bromo-benzaldehyde (203 mg, 1 mmol), 2M aqueous sodium carbonate solution (1 mL, 2 mmol), 2-dicyclohexylphosphino-2?,6?-dimethoxybiphenyl (37 mg, 0.08 mmol) and tris(dibenzylideneacetone)dipalladium (18 mg, 0.02 mmol) were dissolved in 3 mL of a mixture of the solvents ethylene glycol dimethyl ether and toluene (V/V=1:2). The reaction mixture was heated at 100 C. for 2 hours, and then at 120 C. for 0.5 hours under microwave conditions. The resulting mixture was mixed with 10 mL of water and extracted with ethyl acetate (10 mL×3). The combined organic extracts were washed with saturated sodium chloride solution (30 mL), dried with anhydrous magnesium sulphate, and filtered. The filtrate was concentrated under reduced pressure. The residue was purified by silica gel column chromatography with elution system B to obtain the title compound 4?-(benzyloxy)-4-fluoro-2?,6?-dimethylbiphenyl-3-carbaldehyde 18a (390 mg, yield 58.4%) as a colorless slime. MS m/z (ESI): 335.2 [M+1] |
Tags: 2-Fluoro-5-bromobenzaldehyde | Bromides | Ketones | Benzene Compounds | Fluorinated Building Blocks | Aldehydes | Aryls | Organic Building Blocks | 93777-26-5
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H362 | May cause harm to breast-fed children |
H370 | Causes damage to organs |
H371 | May cause damage to organs |
H372 | Causes damage to organs through prolonged or repeated exposure |
H373 | May cause damage to organs through prolonged or repeated exposure |
Environmental hazards | |
Code | Phrase |
H400 | Very toxic to aquatic life |
H401 | Toxic to aquatic life |
H402 | Harmful to aquatic life |
H410 | Very toxic to aquatic life with long-lasting effects |
H411 | Toxic to aquatic life with long-lasting effects |
H412 | Harmful to aquatic life with long-lasting effects |
H413 | May cause long-lasting harmful effects to aquatic life |
H420 | Harms public health and the environment by destroying ozone in the upper atmosphere |
Sorry,this product has been discontinued.
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