Ethyl Acetate → (2S,4R)-N-t-butoxycarbonyl-4-t-butyldimethylsiloxy-2-[alpha-hydroxy-4-(methoxymethoxymethyl)benzyl]pyrrolidine

Participants

Reaction Conditions

Reaction Steps

1.6M n-Butyl lithium-hexane solution (104 ml, 167 mmol) was added dropwise to a solution of 1-bromo-4-(methoxymethoxymethyl)benzene (38.6 g, 167 mmol) in tetrahydrofuran (350 ml) at -78° C. in a nitrogen stream over 30 minutes. This reaction solution was stirred at -78° C. for 30 minutes and then a solution of (2S,4R)-N-t-butoxycarbonyl-4-(t-butyldimethylsiloxy)prolinal (27.5 g, 83.5 mmol) in tetrahydrofuran (300 ml) was added dropwise thereto over 1 hour. This reaction solution was stirred at -70° C. for 2 hours and then warmed and saturated aqueous ammonium chloride was added thereto at -20° C. To the reaction mixture, a liquid mixture of ethyl acetate with water was added. The organic layer was washed successively with dilute hydrochloric acid, saturated aqueous sodium hydrogencarbonate and saturated aqueous sodium chloride, then dried over anhydrous magnesium sulfate, and concentrated in vacuo. The resulting oily residue was subjected to silica gel column chromatography (Wakogel™ C-300, heptane-ethyl acetate=4:1) to give (2S,4R)-N-t-butoxycarbonyl-4-t-butyldimethylsiloxy-2-[α-hydroxy-4-(methoxymethoxymethyl)benzyl]pyrrolidine (24.1 g, yield: 59.8%) as a colorless oily substance.

Provenance & Evidence