反应详情

To a solution of racemic (1S,6R)-6-methyl-7-azabicyclo[4.2.0]octan-8-one (0.46 g, 3.3 mmol) in methanol (9 mL) at 0° C. was added trimethylsilylchloride (0.84 g, 2 eq). The reaction was stirred at room temperature overnight, concentrated and chased with methanol/benzene to afford the crude amino ester. To a solution of the crude amino ester in dichloromethane (10 mL) was added 4-(2-methyl-quinolin-4-ylmethoxy) -benzenesulfonyl chloride hydrochloride (1.5 g, 1.2 eq) followed by saturated sodium bicarbonate and ethyl acetate (2 mL). The reaction was stirred overnight and the methylene chloride was removed in vacuo. The mixture was then extracted with ethyl acetate, washed with brine, dried over MgSO4, filtered and concentrated. Chromatography on silica gel eluting with a gradient of 40-60% ethyl acetate/hexanes afforded racemic methyl (1S,2R)-2-methyl-2-[({4-[(2-methylquinolin-4-yl)methoxy]phenyl}sulfonyl)amino]cyclohexanecarboxylate (0.375 g, 23% over two steps). MS: 483.1 (M+H)+

1. concentrationconcentrated
2. customto afford the crude amino ester
3. stirringThe reaction was stirred overnight
4. customthe methylene chloride was removed in vacuo
5. extractionThe mixture was then extracted with ethyl acetate
6. washwashed with brine
7. dry with materialdried over MgSO4
8. filtrationfiltered
9. concentrationconcentrated