2-氟-5-甲基苯酚

反应条件: temp:0.00; pressure:0.00; stir:

反应条件: temp:0.00; pressure:0.00; stir:

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

实验步骤: 2-Fluoro-5-methylphenol (5.0 g, 40 mmol) was dissolved in chloroform (200 mL). Tetrabutylammonium tribromide (19 g, 40 mmol) was added and the reaction stirred at ambient temperature for 30 minutes. The reaction was concentrated and purified over silica gel (20% EtOAc in hexanes) to afford 4-bromo-2-fluoro-5-methylphenol (7.8 g, 38 mmol, 96% yield) as an amber oil. The reaction was concentrated purified over silica gel (20% EtOAc in hexanes)

反应条件: temp:220.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: To a 500 ml. flask were added 200 grams of pyridine hydrochloride. The flask was fitted with a magnetic stirrer, a reflux condenser, and a nitrogen bubbler. The pyridine salt was heated to about 180° C. to remove any moisture. The salt then was allowed to cool somewhat, and 34 grams (0.243 mole) of the fluorotoluene compound were added. The mixture was heated to 220° C. and maintained there for about 3 hours. The mixture then was cooled, and a large volume of water was added. The reaction mixture then was extracted with several portions of methylene chloride. The methylene chloride extracts were combined, and the solvent was removed in vacuo to obtain a pale yellow product which by nmr analysis indicated the presence of about 5 percent of starting material. The product then was taken up in an excess of 1M sodium hydroxide. The solution was extracted with methylene chloride, and the aqueous layer then was acidified with hydrochloric acid. The acidified portion was extracted with methylene chloride. Evaporation of the methylene chloride extract and distillation of the residue gave 26.6 grams of 2-fluoro-5-methylphenol, b.p.30 86°-93° C. The flask was fitted with a magnetic stirrer, a reflux condenser to remove any moisture to cool somewhat maintained there for about 3 hours The mixture then was cooled The reaction mixture then was extracted with several portions of methylene chloride the solvent was removed in vacuo to obtain a pale yellow product which by nmr analysis The solution was extracted with methylene chloride The acidified portion was extracted with methylene chloride Evaporation of the methylene chloride extract distillation of the residue

反应条件: temp:25.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: A 200 ml 3-neck round bottom flask equipped with a magnetic stirrer bar and a reflux condenser was charged with 4.99 g (40 mmol) of 2-fluoro-5-methyl phenol, 9.01 g (44 mmol) of ethyl 4-bromobutyrate, 6.63 g (48 mmol) potassium carbonate and 120 ml of 2-butanone. The slurry heated to reflux. After stirring for 14.5 hr at reflux, the reaction mixture was cooled to 25° C., filtered and concentrated. The residue was taken up in water (200 ml) and treated with 42 ml (84 mmol) 2N aqueous sodium hydroxide. The reaction mixture was heated to reflux for 2 hours and cooled to 25° C. The yellow solution was acidified with 45 ml 2N aqueous hydrochloric acid. The resulting white solid was isolated by filtration washing with twice with water then twice with hexanes to yield 7.64 g (90%), mp 62-64° C. Combustion analysis: Found: C, 62.2%; H, 6.19%; Calculated: C, 62.26%; H, 6.17%; 1H NMR analysis (d6-DMSO): δ 12.2, broad s, 1H, (COOH); δ7.0, m, 2H (aryl H); δ 6.7, s, 1H (aryl H); δ 4.0, t, 2H (CH2 α ArO); δ 2.4, t, 2H (CH2 α COOH); δ 2.21, s, 3H (CH3 para F); δ 1.90, m, 2H (CH2 β COOH). A 200 ml 3-neck round bottom flask equipped with a magnetic stirrer bar and a reflux condenser The slurry heated to reflux at reflux filtered concentrated The reaction mixture was heated to reflux for 2 hours cooled to 25° C The resulting white solid was isolated by filtration washing with twice with water twice with hexanes to yield 7.64 g (90%), mp 62-64° C

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

实验步骤: 2-fluoro-5-methylphenol (23.8 g, 0.19 mol) and bromine (9.7 ml, 0.19 mol) are combined in 50 ml of glacial acetic acid and stirred at RT for one hour. Acetic acid was removed under vacuum. The liquid was diluted with ethyl acetate and washed with water. The organic layer was washed with brine, dried over anhydrous sodium sulfate, filtered and concentrated to afford 4-bromo-2-fluoro-5-methylphenol (38 g, 98% yield) as a colorless liquid. No [M+H] peak by LCMS. 1H NMR (400 MHz, CHLOROFORM-d) ppm 1.98 (s, 1 H) 2.22 (s, 3 H) 6.81 (dd, J=9.15, 0.54 Hz, 1 H) 7.17 (d, J=9.88 Hz, 1 H) Acetic acid was removed under vacuum The liquid was diluted with ethyl acetate washed with water The organic layer was washed with brine dried over anhydrous sodium sulfate filtered concentrated

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

实验步骤: To a solution of chlorosulfonic acid (1.5 g, 13.3 mmol) dissolved in 10 mL of dichloromethane was added 2-fluoro-5-methylphenol (1.1 g, 8.86 mmol) dropwise. After 10 minutes, the reaction was quenched by adding to ice water. The reaction was extracted with dichloromethane, washed with brine, dried over MgSO4, filtered, and concentrated to give 150 mg (7.5%) of the title compound. the reaction was quenched by adding to ice water The reaction was extracted with dichloromethane washed with brine dried over MgSO4 filtered concentrated

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

实验步骤: To a solution of chlorosulfonic acid (1.5 g, 13.3 mmol) dissolved in 10 mL of dichloromethane was added 2-fluoro-5-methylphenol (1.1 g, 8.86 mmol) dropwise. After 10 minutes, the reaction was quenched by adding to ice water. The reaction was extracted with dichloromethane, washed with brine, dried over MgSO4, filtered, and concentrated to give 150 mg (7.5%) of the title compound. the reaction was quenched by adding to ice water The reaction was extracted with dichloromethane washed with brine dried over MgSO4 filtered concentrated

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

实验步骤: Benzoyl chloride (4.22 g, 30 mmol) was added dropwise with a syringe to a solution of 2-fluoro-5-methylphenol (3.784 g, 30 mmol) and triethylamine (5 mL) in dichloromethane (50 mL), The mixture was stirred for 18 h at room temperature and concentrated under reduced pressure. Diethyl ether (200 mL) and water (100 mL) were added, the organic layer was separated and extracted with 2N NaOH (2×30 mL) and brine (20 mL), dried over sodium sulphate and concentrated under reduced pressure to give a white solid. Yield: 6.601 g (96%). 1H-NMR (400 MHz, CDCl3) δ=2.36 (s, 3H, —CH3), 7.01-7.12 (m, 3H), 7.49-7.55 (m, 2H), 7.63-7.68 (m, 1H), 8.19-8.23 (m, 2H). LRMS (FAB+): 231.1 (100, [M+H]+). concentrated under reduced pressure Diethyl ether (200 mL) and water (100 mL) were added the organic layer was separated extracted with 2N NaOH (2×30 mL) and brine (20 mL) dried over sodium sulphate concentrated under reduced pressure to give a white solid

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

实验步骤: 2-fluoro-5-methylphenol (23.8 g, 0.19 mol) and bromine (9.7 ml, 0.19 mol) are combined in 50 ml of glacial acetic acid and stirred at RT for one hour. Acetic acid was removed under vacuum. The liquid was diluted with ethyl acetate and washed with water. The organic layer was washed with brine, dried over anhydrous sodium sulfate, filtered and concentrated to afford 4-bromo-2-fluoro-5-methylphenol (38 g, 98% yield) as a colorless liquid. No [M+H] peak by LCMS. 1H NMR (400 MHz, CHLOROFORM-d) δ ppm 1.98 (s, 1 H) 2.22 (s, 3 H) 6.81 (dd, J=9.15, 0.54 Hz, 1 H) 7.17 (d, J=9.88 Hz, 1 H) Acetic acid was removed under vacuum The liquid was diluted with ethyl acetate washed with water The organic layer was washed with brine dried over anhydrous sodium sulfate filtered concentrated

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

实验步骤: 2-Fluoro-5-methylphenol (5.0 g, 40 mmol) was dissolved in chloroform (200 mL). Tetrabutylammonium tribromide (19 g, 40 mmol) was added and the reaction stirred at ambient temperature for 30 minutes. The reaction was concentrated and purified over silica gel (20% EtOAc in hexanes) to afford 4-bromo-2-fluoro-5-methylphenol (7.8 g, 38 mmol, 96% yield) as an amber oil. The reaction was concentrated purified over silica gel (20% EtOAc in hexanes)

反应条件: temp:220.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: To a 500 ml. flask were added 200 grams of pyridine hydrochloride. The flask was fitted with a magnetic stirrer, a reflux condenser, and a nitrogen bubbler. The pyridine salt was heated to about 180° C. to remove any moisture. The salt then was allowed to cool somewhat, and 34 grams (0.243 mole) of the fluorotoluene compound were added. The mixture was heated to 220° C. and maintained there for about 3 hours. The mixture then was cooled, and a large volume of water was added. The reaction mixture then was extracted with several portions of methylene chloride. The methylene chloride extracts were combined, and the solvent was removed in vacuo to obtain a pale yellow product which by nmr analysis indicated the presence of about 5 percent of starting material. The product then was taken up in an excess of 1M sodium hydroxide. The solution was extracted with methylene chloride, and the aqueous layer then was acidified with hydrochloric acid. The acidified portion was extracted with methylene chloride. Evaporation of the methylene chloride extract and distillation of the residue gave 26.6 grams of 2-fluoro-5-methylphenol, b.p.30 86°-93° C. The flask was fitted with a magnetic stirrer, a reflux condenser to remove any moisture to cool somewhat maintained there for about 3 hours The mixture then was cooled The reaction mixture then was extracted with several portions of methylene chloride the solvent was removed in vacuo to obtain a pale yellow product which by nmr analysis The solution was extracted with methylene chloride The acidified portion was extracted with methylene chloride Evaporation of the methylene chloride extract distillation of the residue