chloro-dimethyl-propan-2-ylsilane

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: To a solution of (4-amino-5-chloro-2-methoxyphenyl)methanol (intermediate 38; 1.5 g, 0.008 mol) in dimethylformamide (35 mL) was added imidazole (1.7 g, 0.02 mol). The mixture was cooled to 0° C. and chloro(isopropyl)dimethylsilane (2.5 g, 0.01 mol) was added dropwise. The reaction was stirred overnight at room temperature. The solvent was removed and the crude was partitioned between water and hexane, the organic layer was washed with water, sodium bicarbonate 4% and brine, dried, filtered and evaporated to dryness. The crude obtained was purified by column chromatography with silica gel, eluting with hexane/ethyl acetate (from 8/1 to 4/1). The title compound was obtained as a yellow solid (58%). The solvent was removed the crude was partitioned between water and hexane the organic layer was washed with water, sodium bicarbonate 4% and brine dried filtered evaporated to dryness The crude obtained was purified by column chromatography with silica gel eluting with hexane/ethyl acetate (from 8/1 to 4/1)

反応条件: temp:0.00; pressure:0.00; stir:

反応条件: temp:-78.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: 1,4-Dibromo-benzene (1.18 g, 5 mmol) was dissolved in THF (15 ml) and cooled to −78° C. Under argon a 1.6 M solution of n-butyl lithium in hexane (3.13 ml, 5 mmol) was added slowly under stirring keeping the temperature below −70° C. After complete addition the reaction was stirred at −78° C. for 30 min and dimethyl-isopropyl-silylchloride (683 mg, 5 mmol) was added carefully keeping the temperature again below −70° C. The reaction was stirred at −78° C. for 30 min and a 1.6 M solution of n-butyl lithium in hexane (3.13 ml, 5 mmol) was added at this temperature keeping the temperature below −70° C. After stirring for 30 min at −78° C. DMF (1.1 g, 15 mmol) was added in one portion and the reaction was allowed to warm to rt. Water was added and the solvent was evaporated. The reaction was extracted twice with diethylether. The combined organic layers were dried over sodium sulfate, filtered and the solvent was evaporated, to yield 4-(isopropyl-dimethyl-silanyl)-benzaldehyde (900 mg, 87%) as a colorless oil. The product was pure enough to be used directly in the next step. MS (ISP): 207.1 (M+H)+. 1HNMR (CDCl3, 300 MHz): δ 10.0 (s, 1H), 7.84 (d, J=8.1 Hz, 2H), 7.67 (d, J=8.1 Hz, 2H), 0.93-0.99 (m, 7H), 0.28 (s, 6H). the temperature below −70° C After complete addition the reaction was stirred at −78° C. for 30 min the temperature again below −70° C The reaction was stirred at −78° C. for 30 min the temperature below −70° C After stirring for 30 min at −78° C to warm to rt the solvent was evaporated The reaction was extracted twice with diethylether The combined organic layers were dried over sodium sulfate filtered the solvent was evaporated

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

実験手順: One g of diisopropyl amine was dissolved in 7.5 ml of THF at 0° C., and 7 ml of a 1.6M BuLi hexane solution was dropwise added. The mixture was stirred for 15 minutes at 0° C. The reaction solution was cooled to -78° C., and then 0.88 g (10 mmol) of methyl propionate was added. Thirty minutes later, 1.64 g (12 mmol) of dimethyl isopropyl silyl chloride was added thereto, and the mixture was stirred for 30 minutes. To the reaction solution, 1.9 ml of methyl iodide and 5 ml of pentane were added at -78° C., and then the reaction mixture was stirred at 0° C. for 30 minutes by means of ice bath. Then, the reaction mixture was left to stand overnight in a refrigerator. The reaction mixture was subjected to filtration, and the filtrate was distilled under reduced pressure, whereby 1.24 g (66%) of crude methylketene methyl dimethylisopropylsilyl acetal was obtained. NMR(CCl4)δ(ppm): 0.12(6H, s, (CH3)2Si), 0.96(6H, s, CH(CH3)2), 0.99(1H, s, CH(CH3)2), 1.40(3H, d, J=6 Hz, =CHCH3), 3.45(3H, s, OCH3), 3.57(1H, q, J=6 Hz, CH3CH=). The reaction solution was cooled to -78° C. the mixture was stirred for 30 minutes the reaction mixture was stirred at 0° C. for 30 minutes by means of ice bath Then, the reaction mixture was left to stand overnight in a refrigerator The reaction mixture was subjected to filtration the filtrate was distilled under reduced pressure

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

実験手順: To a solution of (4-amino-5-chloro-2-methoxyphenyl)methanol (intermediate 38; 1.5 g, 0.008 mol) in dimethylformamide (35 mL) was added imidazole (1.7 g, 0.02 mol). The mixture was cooled to 0° C. and chloro(isopropyl)dimethylsilane (2.5 g, 0.01 mol) was added dropwise. The reaction was stirred overnight at room temperature. The solvent was removed and the crude was partitioned between water and hexane, the organic layer was washed with water, sodium bicarbonate 4% and brine, dried, filtered and evaporated to dryness. The crude obtained was purified by column chromatography with silica gel, eluting with hexane/ethyl acetate (from 8/1 to 4/1). The title compound was obtained as a yellow solid (58%). The solvent was removed the crude was partitioned between water and hexane the organic layer was washed with water, sodium bicarbonate 4% and brine dried filtered evaporated to dryness The crude obtained was purified by column chromatography with silica gel eluting with hexane/ethyl acetate (from 8/1 to 4/1)