Chlorotrimethylsilane → racemic methyl (1S,2R)-2-methyl-2-[({4-[(2-methylquinolin-4-yl)methoxy]phenyl}sulfonyl)amino]cyclohexanecarboxylate

Participants

Reaction Steps

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)+

Provenance & Evidence