3-fluoro-5-methoxyphenol

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Boron tribromide (1M in dichloromethane, 9 mL, 89.985 mmol) was added drop wise to an ice-cooled solution of 3,5-dimethoxy fluorobenzene (3 ml, 22.496 mmol) in dichloromethane (20 mL) and the mixture was stirred at 0° C. to room temperature for 4 hours. The solution was cooled to 0° C., further boron tribromide (4 ml, 44.992 mmol) was added and stirring continued, warming to room temperature for an additional 18 hours. The reaction was quenched with 0.88 ammonia solution and stirred at room temperature for 90 minutes. The organic layer was separated and extracted with 2N sodium hydroxide (30 ml), which was then acidified to pH1 by drop wise addition of concentrated hydrochloric acid. The aqueous layer was then re-extracted with dichloromethane (3×15 mL), the combined organic solution was dried over sodium sulfate and concentrated in vacuo to afford the title compound as a white solid in 54% yield, 1.72 g. stirring warming to room temperature for an additional 18 hours The reaction was quenched with 0.88 ammonia solution stirred at room temperature for 90 minutes The organic layer was separated extracted with 2N sodium hydroxide (30 ml), which was then acidified to pH1 by drop wise addition of concentrated hydrochloric acid The aqueous layer was then re-extracted with dichloromethane (3×15 mL) the combined organic solution was dried over sodium sulfate concentrated in vacuo

Conditions: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Boron tribromide (1M in dichloromethane, 9 mL, 89.985 mmol) was added drop wise to an ice-cooled solution of 3,5-dimethoxy fluorobenzene (3 ml, 22.496 mmol) in dichloromethane (20 mL) and the mixture was stirred at 0° C. to room temperature for 4 hours. The solution was cooled to 0° C., further boron tribromide (4 ml, 44.992 mmol) was added and stirring continued, warming to room temperature for an additional 18 hours. The reaction was quenched with 0.88 ammonia solution and stirred at room temperature for 90 minutes. The organic layer was separated and extracted with 2N sodium hydroxide (30 ml), which was then acidified to pH1 by drop wise addition of concentrated hydrochloric acid. The aqueous layer was then re-extracted with dichloromethane (3×15 mL), the combined organic solution was dried over sodium sulfate and concentrated in vacuo to afford the title compound as a white solid in 54% yield, 1.72 g. stirring warming to room temperature for an additional 18 hours The reaction was quenched with 0.88 ammonia solution stirred at room temperature for 90 minutes The organic layer was separated extracted with 2N sodium hydroxide (30 ml), which was then acidified to pH1 by drop wise addition of concentrated hydrochloric acid The aqueous layer was then re-extracted with dichloromethane (3×15 mL) the combined organic solution was dried over sodium sulfate concentrated in vacuo

Conditions: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Boron tribromide (1M in dichloromethane, 9 mL, 89.985 mmol) was added drop wise to an ice-cooled solution of 3,5-dimethoxy fluorobenzene (3 ml, 22.496 mmol) in dichloromethane (20 mL) and the mixture was stirred at 0° C. to room temperature for 4 hours. The solution was cooled to 0° C., further boron tribromide (4 ml, 44.992 mmol) was added and stirring continued, warming to room temperature for an additional 18 hours. The reaction was quenched with 0.88 ammonia solution and stirred at room temperature for 90 minutes. The organic layer was separated and extracted with 2N sodium hydroxide (30 ml), which was then acidified to pH1 by drop wise addition of concentrated hydrochloric acid. The aqueous layer was then re-extracted with dichloromethane (3×15 mL), the combined organic solution was dried over sodium sulfate and concentrated in vacuo to afford the title compound as a white solid in 54% yield, 1.72 g. stirring warming to room temperature for an additional 18 hours The reaction was quenched with 0.88 ammonia solution stirred at room temperature for 90 minutes The organic layer was separated extracted with 2N sodium hydroxide (30 ml), which was then acidified to pH1 by drop wise addition of concentrated hydrochloric acid The aqueous layer was then re-extracted with dichloromethane (3×15 mL) the combined organic solution was dried over sodium sulfate concentrated in vacuo

Conditions: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Boron tribromide (1M in dichloromethane, 9 mL, 89.985 mmol) was added drop wise to an ice-cooled solution of 3,5-dimethoxy fluorobenzene (3 ml, 22.496 mmol) in dichloromethane (20 mL) and the mixture was stirred at 0° C. to room temperature for 4 hours. The solution was cooled to 0° C., further boron tribromide (4 ml, 44.992 mmol) was added and stirring continued, warming to room temperature for an additional 18 hours. The reaction was quenched with 0.88 ammonia solution and stirred at room temperature for 90 minutes. The organic layer was separated and extracted with 2N sodium hydroxide (30 ml), which was then acidified to pH1 by drop wise addition of concentrated hydrochloric acid. The aqueous layer was then re-extracted with dichloromethane (3×15 mL), the combined organic solution was dried over sodium sulfate and concentrated in vacuo to afford the title compound as a white solid in 54% yield, 1.72 g. stirring warming to room temperature for an additional 18 hours The reaction was quenched with 0.88 ammonia solution stirred at room temperature for 90 minutes The organic layer was separated extracted with 2N sodium hydroxide (30 ml), which was then acidified to pH1 by drop wise addition of concentrated hydrochloric acid The aqueous layer was then re-extracted with dichloromethane (3×15 mL) the combined organic solution was dried over sodium sulfate concentrated in vacuo

Conditions: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Boron tribromide (1M in dichloromethane, 9 mL, 89.985 mmol) was added drop wise to an ice-cooled solution of 3,5-dimethoxy fluorobenzene (3 ml, 22.496 mmol) in dichloromethane (20 mL) and the mixture was stirred at 0° C. to room temperature for 4 hours. The solution was cooled to 0° C., further boron tribromide (4 ml, 44.992 mmol) was added and stirring continued, warming to room temperature for an additional 18 hours. The reaction was quenched with 0.88 ammonia solution and stirred at room temperature for 90 minutes. The organic layer was separated and extracted with 2N sodium hydroxide (30 ml), which was then acidified to pH1 by drop wise addition of concentrated hydrochloric acid. The aqueous layer was then re-extracted with dichloromethane (3×15 mL), the combined organic solution was dried over sodium sulfate and concentrated in vacuo to afford the title compound as a white solid in 54% yield, 1.72 g. stirring warming to room temperature for an additional 18 hours The reaction was quenched with 0.88 ammonia solution stirred at room temperature for 90 minutes The organic layer was separated extracted with 2N sodium hydroxide (30 ml), which was then acidified to pH1 by drop wise addition of concentrated hydrochloric acid The aqueous layer was then re-extracted with dichloromethane (3×15 mL) the combined organic solution was dried over sodium sulfate concentrated in vacuo

Conditions: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Boron tribromide (1M in dichloromethane, 9 mL, 89.985 mmol) was added drop wise to an ice-cooled solution of 3,5-dimethoxy fluorobenzene (3 ml, 22.496 mmol) in dichloromethane (20 mL) and the mixture was stirred at 0° C. to room temperature for 4 hours. The solution was cooled to 0° C., further boron tribromide (4 ml, 44.992 mmol) was added and stirring continued, warming to room temperature for an additional 18 hours. The reaction was quenched with 0.88 ammonia solution and stirred at room temperature for 90 minutes. The organic layer was separated and extracted with 2N sodium hydroxide (30 ml), which was then acidified to pH1 by drop wise addition of concentrated hydrochloric acid. The aqueous layer was then re-extracted with dichloromethane (3×15 mL), the combined organic solution was dried over sodium sulfate and concentrated in vacuo to afford the title compound as a white solid in 54% yield, 1.72 g. stirring warming to room temperature for an additional 18 hours The reaction was quenched with 0.88 ammonia solution stirred at room temperature for 90 minutes The organic layer was separated extracted with 2N sodium hydroxide (30 ml), which was then acidified to pH1 by drop wise addition of concentrated hydrochloric acid The aqueous layer was then re-extracted with dichloromethane (3×15 mL) the combined organic solution was dried over sodium sulfate concentrated in vacuo

Conditions: temp:60.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A 0° C. solution of 3-fluoro-5-methoxy-phenol (2.40 g, 16.9 mmol) in dry DMF (20 mL) is treated with a 60% suspension of NaH (0.74 g, 18.5 mmol) and then stirred for 15 minutes under N2. A solution of 4-fluoro-2-methyl-benzaldehyde (2.33 g, 16.9 mmol) in DMF (10 mL) is added dropwise, and the mixture is warmed to 60° C. for 4 hours. The mixture is cooled and acidified with 1 N HCl. The mixture is then diluted with Et2O and extracted with water. The organic layer is dried (Na2SO4), and the solvent is removed in vacuo to afford crude product that is absorbed on silica gel and purified by flash chromatography using 6/1 hexanes/ethyl acetate to afford 1.40 g (32%) of the title compound. Rf=0.41 (2/1 hexanes/EtOAc). 1H NMR (400 MHz, CDCl3); MS (ES+) m/z mass calculated for C15H13O3F 260, found 261 (M+1, 100%). The mixture is cooled extracted with water The organic layer is dried (Na2SO4) the solvent is removed in vacuo to afford crude product that is absorbed on silica gel purified by flash chromatography

Conditions: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A −78° C. solution of 1-fluoro-3,5-dimethoxybenzene (4.98 g, 31.9 mmol) in dry CH2Cl2 (50 mL) is treated with a 1 M CH2Cl2 solution of boron tribromide (128 mL, 128 mmol), and the mixture is warmed to 0° C. and stirred under N2. Upon completion, the mixture is poured into ice water and extracted with Et2O. The organic layer is dried (Na2SO4), and the solvent is removed in vacuo to afford crude product that is absorbed on silica gel and purified by flash chromatography using a gradient of 5/1 to 1/1 to hexanes/ethyl acetate to afford 2.40 g (53%) of the title compound. Rf=0.49 (1/1 hexanes/EtOAc). 1H NMR (400 MHz, CDCl3). MS (ES−) m/z mass calculated for C7H7O2F 142, found 141 (M−1, 100%). extracted with Et2O The organic layer is dried (Na2SO4) the solvent is removed in vacuo to afford crude product that is absorbed on silica gel purified by flash chromatography

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Under a nitrogen atmosphere, 3-fluoro-5-methoxyphenol (50-1) (15 g, 106 mmol) was diluted in DCE (150 mL, 0.7 M). To this solution NCS (15.5 g, 116 mmol) was added, and the reaction mixture was heated to reflux for 4 hours. The reaction was then cooled to room temperature and quenched with water (100 mL). The aqueous layer was then extracted with methylene chloride (3×50 mL). The organic extracts were dried over sodium sulfate and concentrated. Silica gel chromatography (1%-30% EtOAc/Hexanes) gave 2-chloro-3-fluoro-5-methoxyphenol (50-2) (6.7 g, 36%) and 4-chloro-3-fluoro-5-methoxyphenol (50-3) (2.8 g, 15%). LCMS (ES) m/z 177.2 (M)+. The starting material, 3-fluoro-5-methoxyphenol (50-1), was also recovered (4.3 g). the reaction mixture was heated to reflux for 4 hours quenched with water (100 mL) The aqueous layer was then extracted with methylene chloride (3×50 mL) The organic extracts were dried over sodium sulfate concentrated

Conditions: temp:-15.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Under nitrogen atmosphere, 1-fluoro-3,5-dimethoxybenzene (25 g, 160 mmol) was diluted in CH2Cl2 (200 mL, 0.8M) and then cooled to −15° C. Next, BBr3 (176 mL, 176 mmol, 1M in CH2Cl2) was slowly added to the reaction mixture. The reaction mixture was stirred at −15° C. for one and a half hours and at room temperature for 10 minutes. The reaction mixture was then cooled to 0° C. and slowly quenched with water (150 mL). The aqueous layer was then extracted with methylene chloride (3×100 mL). The organic extracts were dried over sodium sulfate and concentrated. Silica gel chromatography (1%-30% EtOAc/Hexanes) gave the mono demethylated product (50-1) (15 g, 67%). The reaction mixture was then cooled to 0° C. slowly quenched with water (150 mL) The aqueous layer was then extracted with methylene chloride (3×100 mL) The organic extracts were dried over sodium sulfate concentrated

Conditions: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Boron tribromide (1M in dichloromethane, 9 mL, 89.985 mmol) was added drop wise to an ice-cooled solution of 3,5-dimethoxy fluorobenzene (3 ml, 22.496 mmol) in dichloromethane (20 mL) and the mixture was stirred at 0° C. to room temperature for 4 hours. The solution was cooled to 0° C., further boron tribromide (4 ml, 44.992 mmol) was added and stirring continued, warming to room temperature for an additional 18 hours. The reaction was quenched with 0.88 ammonia solution and stirred at room temperature for 90 minutes. The organic layer was separated and extracted with 2N sodium hydroxide (30 ml), which was then acidified to pH1 by drop wise addition of concentrated hydrochloric acid. The aqueous layer was then re-extracted with dichloromethane (3×15 mL), the combined organic solution was dried over sodium sulfate and concentrated in vacuo to afford the title compound as a white solid in 54% yield, 1.72 g. stirring warming to room temperature for an additional 18 hours The reaction was quenched with 0.88 ammonia solution stirred at room temperature for 90 minutes The organic layer was separated extracted with 2N sodium hydroxide (30 ml), which was then acidified to pH1 by drop wise addition of concentrated hydrochloric acid The aqueous layer was then re-extracted with dichloromethane (3×15 mL) the combined organic solution was dried over sodium sulfate concentrated in vacuo