反应详情

To a solution of ethyl 3-((tert-butyldiphenylsilyl)oxy)bicyclo[3.1.0]hexane-6-carboxylate (70.0 g, 171 mmol) in ethanol (400 mL) was slowly added a solution of sodium hydroxide (20.56 g, 513.94 mmol) in water (100 mL). After 20 h, the reaction mixture was concentrated and the resulting residue was diluted with water (200 mL). The aqueous solution was adjusted to pH=3 by dropwise addition of 3 M aqueous hydrochloric acid. The aqueous mixture was extracted with ethyl acetate (2×200 mL). The combined organics were washed with saturated aqueous sodium chloride (200 mL), dried over anhydrous sodium sulfate, filtered, and concentrated to yield 3-((tert-butyldiphenylsilyl)oxy)bicyclo[3.1.0]hexane-6-carboxylic acid as a yellow solid (53 g). To an ice-cooled suspension of crude acid in dichloromethane (600 mL) was added carbonyldiimidazole (25.5 g, 158 mmol). After 2 h, N, O-dimethylhydroxylamine hydrochloride (32 g, 0.33 mmol) was added. After 3 h, the reaction mixture was filtered and the filtrate was concentrated. Purified by flash column chromatography (6:1 petroleum ether/ethyl acetate) afforded 3-((tert-butyldiphenylsilyl)oxy)-N-methoxy-N-methylbicyclo[3.1.0]hexane-6-carboxamide (37 g, 60%) as a colorless oil. 1H NMR (400 MHz, CDCl3): δ 7.63-7.61 (m, 4H), 7.42-7.33 (m, 6H), 4.33-4.31 (m, 1H), 3.74 (s, 2H), 3.57 (s, 1H), 3.21 (s, 2H), 3.10 (s, 1H), 2.21-2.18 (m, 1H), 2.00-1.80 (m, 6H), 1.06-1.01 (m, 9H).

1. concentrationthe reaction mixture was concentrated
2. additionthe resulting residue was diluted with water (200 mL)
3. additionThe aqueous solution was adjusted to pH=3 by dropwise addition of 3 M aqueous hydrochloric acid
4. extractionThe aqueous mixture was extracted with ethyl acetate (2×200 mL)
5. washThe combined organics were washed with saturated aqueous sodium chloride (200 mL)
6. dry with materialdried over anhydrous sodium sulfate
7. filtrationfiltered
8. concentrationconcentrated