4-bromo-2-chloro-5-methoxyaniline

反応条件: temp:0.00; pressure:0.00; stir:

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: A stirred solution of 9.7 g (0.050 mole) of 2-chloro-5-methoxyaniline hydrochloride in 120 mL of acetic acid was cooled to 15° C. To this cold mixture was added 4.0 g (0.025 mole) of bromine. After complete addition, the mixture was allowed to warm to room temperature and was stirred for approximately 18 hours. The mixture was poured into ice water. To the resultant mixture was added a solution of 2.0 g (0.05 mole) of sodium hydroxide in 10 mL of water. This mixture was extracted with 200 mL of diethyl ether. The ether extract was dried over anhydrous magnesium sulfate, filtered, and the filtrate evaporated under reduced pressure to leave an oil. The oil was purified by column chromatography on silica gel, eluting with methylene chloride, to yield 7.3 g of 4-bromo-2-chloro-5-methoxyaniline as a solid, mp 40°-41° C. After complete addition This mixture was extracted with 200 mL of diethyl ether The ether extract was dried over anhydrous magnesium sulfate filtered the filtrate evaporated under reduced pressure to leave an oil The oil was purified by column chromatography on silica gel eluting with methylene chloride

反応条件: temp:0.00; pressure:0.00; stir:

反応条件: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: Isopropylmagnesium chloride (2M in tetrahydrofuran, 23 ml, 46 mmol) (commercially available, for example, from Aldrich) was added over 5 minutes to a stirred solution of 4-bromo-2-chloro-5-methoxyaniline (Step A) (10 g, 42 mmol) in tetrahydrofuran (70 ml) at −10° C. The resulting solution was allowed to warm to 0° C. over 50 minutes to give a thick slurry, then cooled to −25° C. and n-butyllithium (1.6M in hexanes, 90 ml, 144 mmol) was added over 20 minutes followed by tetrahydrofuran (20 ml). The solution was warmed to −10° C. over 30 minutes and then N,N-dimethylformamide (16 ml, 207 mmol) was added over 5 minutes and the resulting thick slurry was warmed to 0° C. over 20 minutes. A solution of citric acid (22 g, 105 mmol) in water (50 ml) was added cautiously over 15 minutes keeping reaction at <10° C. The slurry was aged at 20° C. for 30 minutes then filtered under vacuum. The cake was washed with water (100 ml) and then dried under vacuum at 40° C. for 16 hours to give 4-amino-5-chloro-2-methoxybenzaldehyde (6.1 g, 80% th) as a pale yellow solid. to give a thick slurry cooled to −25° C. The solution was warmed to −10° C. over 30 minutes the resulting thick slurry was warmed to 0° C. over 20 minutes reaction at <10° C then filtered under vacuum The cake was washed with water (100 ml) dried under vacuum at 40° C. for 16 hours

反応条件: temp:-5.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: 1,3-Dibromo-5,5-dimethylhydantoin (commercially available, for example, from Aldrich) (9.1 g, 32 mmol) was added over 20 minutes to a stirred solution of 6-chloro-3-methoxyaniline (commercially available, for example, from Apollo Scientific) (10.0 g, 63 mmol) in ethyl acetate (150 ml) at −5° C. The resulting solution was stirred at −5° C. for 1 hour then washed with a solution of potassium carbonate (6 g, 43 mmol) in water (40 ml and then with water (20 ml). The resulting solution was concentrated under reduced pressure to give 4-bromo-2-chloro-5-methoxyaniline as a pale brown solid (14.3 g, 95%). at −5° C The resulting solution was concentrated under reduced pressure

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: A stirred solution of 9.7 g (0.050 mole) of 2-chloro-5-methoxyaniline hydrochloride in 120 mL of acetic acid was cooled to 15° C. To this cold mixture was added 4.0 g (0.025 mole) of bromine. After complete addition, the mixture was allowed to warm to room temperature and was stirred for approximately 18 hours. The mixture was poured into ice water. To the resultant mixture was added a solution of 2.0 g (0.05 mole) of sodium hydroxide in 10 mL of water. This mixture was extracted with 200 mL of diethyl ether. The ether extract was dried over anhydrous magnesium sulfate, filtered, and the filtrate evaporated under reduced pressure to leave an oil. The oil was purified by column chromatography on silica gel, eluting with methylene chloride, to yield 7.3 g of 4-bromo-2-chloro-5-methoxyaniline as a solid, mp 40°-41° C. After complete addition This mixture was extracted with 200 mL of diethyl ether The ether extract was dried over anhydrous magnesium sulfate filtered the filtrate evaporated under reduced pressure to leave an oil The oil was purified by column chromatography on silica gel eluting with methylene chloride