1-(5-CHLORO-4-FLUORO-2-HYDROXY-PHENYL)-ETHANONE

反应条件: temp:120.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: To 1-(4-fluoro-2-hydroxyphenyl)ethanone (1.7 g, 11.03 mmol) in glacial acetic acid (24 mL) at 10° C. was slowly added sulfuryl chloride (2.23 g, 16.54 mmol). The mixture was heated to 120° C. and was allowed to stir for overnight. The solution was cooled down to room temperature and poured into water (30 mL). The water layer was extracted with EtOAc for three times. The EtOAc was washed with satd. Aq NaHCO3, water, brine, dried (Na2SO4) and concentrated recrystallized The mix was purified by column chromatography using 1:10 Hexanes:Ethyl acetate to yield 234 mg of 1-(5-chloro-4-fluoro-2-hydroxyphenyl)ethanone and 400 mg of 1-(3-chloro-4-fluoro-2-hydroxyphenyl)ethanone. These compounds were used in the next step without characterization. at 10° C. The solution was cooled down to room temperature The water layer was extracted with EtOAc for three times The EtOAc was washed with satd Aq NaHCO3, water, brine, dried (Na2SO4) concentrated recrystallized The mix was purified by column chromatography

反应条件: temp:70.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: A solution of 1-(5-chloro-4-fluoro-2-hydroxyphenyl)ethanone (23.8 g, 126 mmol) in acetic acid (100 mL) was treated with N-iodosuccinimide (34.1 g, 151 mmol) and stirred at 70° C. for 2 hr. The reaction mixture was concentrated, diluted with EtOAc and quenched with sat. NaHCO3 solution until the bubbling stopped. The organic layers were separated, washed with water, dried over MgSO4 and stripped to give the desired product which was used in the next step without further purification. The reaction mixture was concentrated diluted with EtOAc quenched with sat. NaHCO3 solution until the bubbling The organic layers were separated washed with water dried over MgSO4

反应条件: temp:60.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: To 4-chloro-3-fluorophenol (from Aldrich, 20 g, 100 mmol) was added acetyl chloride (14.1 mL, 199 mmol) under N2 with stirring. The resulting mixture turned into a clear solution at room temperature quickly and it was heated at 60° C. for 2 hours. To the resultant mixture was added aluminum trichloride (25.0 g, 187 mmol) in portions and the reaction mixture was heated at 180° C. for 30 minutes. The solids slowly dissolved at high temperature. The reaction mixture was then cooled to room temperature while the flask was swirled carefully in order for the solid to form a thin layer inside the flask and then slowly quenched with 1.0 N HCl (300 mL) while cooling in an ice-bath and stirred overnight. The yellow precipitate was washed with water and dried under vacuum to give the desired product as a yellow solid (23.8 g), which was directly used in the next step without further purification. turned into a clear solution at room temperature the reaction mixture was heated at 180° C. for 30 minutes The solids slowly dissolved at high temperature The reaction mixture was then cooled to room temperature while the flask to form a thin layer inside the flask slowly quenched with 1.0 N HCl (300 mL) while cooling in an ice-bath stirred overnight The yellow precipitate was washed with water dried under vacuum

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: To a stirred solution of 1-(5-chloro-4-fluoro-2-hydroxyphenyl)ethanone (8.0 g, 42 mmol) in acetic acid (80 mL) was added N-bromosuccinimide (9.0 g, 50 mmol) and the resulting mixture was stirred at room temperature for 18 hours. The reaction mixture was concentrated, neutralized with saturated sodium bicarbonate solution and extracted with EtOAc. The combined organic layers were washed with brine, dried over sodium sulfate, and then concentrated to dryness under reduced pressure. The residue was purified on silica gel, eluting with 0 to 20% EtOAc in hexane, to yield the desired product (10.5 g, 93%). LCMS calculated for C8H6BrClFO2 (M+H)+: m/z=266.9, 268.9. found: 267.1, 269.1. The reaction mixture was concentrated extracted with EtOAc The combined organic layers were washed with brine dried over sodium sulfate concentrated to dryness under reduced pressure The residue was purified on silica gel eluting with 0 to 20% EtOAc in hexane

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: To a stirred solution of 1-(5-chloro-4-fluoro-2-hydroxyphenyl)ethanone (8.0 g, 42 mmol) in acetic acid (80 mL) was added N-bromosuccinimide (9.0 g, 50 mmol) and the resulting mixture was stirred at room temperature for 18 hours. The reaction mixture was concentrated, neutralized with saturated sodium bicarbonate solution and extracted with EtOAc. The combined organic layers were washed with brine, dried over sodium sulfate, and then concentrated to dryness under reduced pressure. The residue was purified on silica gel, eluting with 0 to 20% EtOAc in hexane, to yield the desired product (10.5 g, 93%). LCMS calculated for C8H6BrClFO2 (M+H)+: m/z=266.9, 268.9. found: 267.1, 269.1. The reaction mixture was concentrated extracted with EtOAc The combined organic layers were washed with brine dried over sodium sulfate concentrated to dryness under reduced pressure The residue was purified on silica gel eluting with 0 to 20% EtOAc in hexane

反应条件: temp:60.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: Acetyl chloride (3.6 mL, 51 mmol) was added to 4-chloro-3-fluorophenol (5.1 g, 35 mmol) and the resulting mixture was heated at 60° C. for 2 hours. Aluminum trichloride (7.0 g, 52 mmol) was added and the mixture was heated at 180° C. for 30 minutes. The mixture was cooled to room temperature. The mixture was cooled to 0° C. and 1 N HCl solution (100 mL) was added dropwise over 30 minutes. The precipitate was washed well with water and dried under vacuum to give the desired compound (6.6 g, 100%). the mixture was heated at 180° C. for 30 minutes The mixture was cooled to room temperature The mixture was cooled to 0° C. The precipitate was washed well with water dried under vacuum

反应条件: temp:70.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: A solution of 1-(5-chloro-4-fluoro-2-hydroxyphenyl)ethanone (23.8 g, 126 mmol) in acetic acid (100 mL) was treated with N-iodosuccinimide (34.1 g, 151 mmol) and stirred at 70° C. for 2 hours. The reaction mixture was concentrated, diluted with EtOAc and quenched with sat. NaHCO3 solution. The organic layer was separated, washed with water, dried over MgSO4 and concentrated under reduced pressure to give the desired product to be used in the next step without further purification. The reaction mixture was concentrated diluted with EtOAc quenched with sat. NaHCO3 solution The organic layer was separated washed with water dried over MgSO4 concentrated under reduced pressure

反应条件: temp:70.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: A solution of 1-(5-chloro-4-fluoro-2-hydroxyphenyl)ethanone (23.8 g, 126 mmol) in acetic acid (100 mL) was treated with N-iodosuccinimide (34.1 g, 151 mmol) and stirred at 70° C. for 2 hours. The reaction mixture was concentrated, diluted with EtOAc and quenched with sat. NaHCO3 solution. The organic layer was separated, washed with water, dried over MgSO4 and concentrated under reduced pressure to give the desired product to be used in the next step without further purification. The reaction mixture was concentrated diluted with EtOAc quenched with sat. NaHCO3 solution The organic layer was separated washed with water dried over MgSO4 concentrated under reduced pressure

反应条件: temp:60.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: To 4-chloro-3-fluorophenol (20 g, 100 mmol, from Aldrich) was added acetyl chloride (14.1 mL, 199 mmol) under N2 with stirring. The resulting mixture turned into a clear solution at room temperature and was heated at 60° C. for 2 hours. To the resultant mixture was added aluminum trichloride (25.0 g, 187 mmol) in portions and the mixture was heated at 180° C. for 30 minutes. The solids slowly dissolved at high temp. The reaction mixture was then cooled to room temperature while the flask was swirled carefully in order for the solid to form a thin layer inside the flask and then slowly quenched with 1.0 N HCl (300 mL) while cooling in an ice-bath and stirred overnight. The yellow precipitate was washed well with water and dried under vacuum to give the desired product as a yellow solid (23.8 g), which was directly used in the next step without further purification. turned into a clear solution at room temperature the mixture was heated at 180° C. for 30 minutes The solids slowly dissolved at high temp The reaction mixture was then cooled to room temperature while the flask to form a thin layer inside the flask slowly quenched with 1.0 N HCl (300 mL) while cooling in an ice-bath stirred overnight The yellow precipitate was washed well with water dried under vacuum

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: To a stirred solution of 1-(5-chloro-4-fluoro-2-hydroxyphenyl)ethanone (7.9 g, 42 mmol) in acetic acid (80 mL, 1.0 mol) was added N-bromosuccinimide (9.0 g, 50 mmol) and the resulting mixture was stirred at rt for 18 h. The reaction mixture was concentrated in vacuo, neutralized with saturated sodium bicarbonate and extracted with ethyl acetate. The combined organic layers were washed with brine, dried over sodium sulfate, and concentrated to dryness under reduced pressure. The residue was purified on silica gel, eluting with 0 to 20% ethyl acetate in hexane, to yield the desired product (93% yield). 1H NMR (300 MHz, CDCl3): δ 13.15 (s, 1H), 7.79 (m, 1H), 2.62 (s, 3H). The reaction mixture was concentrated in vacuo extracted with ethyl acetate The combined organic layers were washed with brine dried over sodium sulfate concentrated to dryness under reduced pressure The residue was purified on silica gel eluting with 0 to 20% ethyl acetate in hexane

反应条件: temp:60.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: To 4-chloro-3-fluorophenol (Oakwood #004459, 5.1 g, 35 mmol) was added acetyl chloride (3.6 mL, 51 mmol) and the resulting mixture was heated at 60° C. for 2 hours. Aluminum trichloride (7.0 g, 52 mmol) was added and the mixture was heated at 180° C. for 30 minutes. The reaction mixture was then cooled to room temperature and slowly quenched with 1M HCl while cooling in an ice-bath and stirred for 30 minutes. The precipitate was washed well with water and dried under vacuum to give the desired product (quantitative). This material was used without further purification. 1H NMR (300 MHz, CDCl3): δ 12.41 (s, 1H), 7.80 (m, 1H), 6.79 (m, 1H), 2.60 (s, 3H). the mixture was heated at 180° C. for 30 minutes The reaction mixture was then cooled to room temperature slowly quenched with 1M HCl while cooling in an ice-bath The precipitate was washed well with water dried under vacuum

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: To a stirred solution of 1-(5-chloro-4-fluoro-2-hydroxyphenyl)ethanone (7.9 g, 42 mmol) in acetic acid (80 mL, 1.0 mol) was added N-bromosuccinimide (9.0 g, 50 mmol) and the resulting mixture was stirred at rt for 18 h. The reaction mixture was concentrated in vacuo, neutralized with saturated sodium bicarbonate and extracted with ethyl acetate. The combined organic layers were washed with brine, dried over sodium sulfate, and concentrated to dryness under reduced pressure. The residue was purified on silica gel, eluting with 0 to 20% ethyl acetate in hexane, to yield the desired product (93% yield). 1H NMR (300 MHz, CDCl3): δ 13.15 (s, 1H), 7.79 (m, 1H), 2.62 (s, 3H). The reaction mixture was concentrated in vacuo extracted with ethyl acetate The combined organic layers were washed with brine dried over sodium sulfate concentrated to dryness under reduced pressure The residue was purified on silica gel eluting with 0 to 20% ethyl acetate in hexane