Water → (3R,4S)-1-Benzyl-4-methylpyrrolidine-3-carbonitrile

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Reaction Steps

(3R,4S)-1-Benzyl-3-hydroxy-4-methylpyrrolidine (4.00 g) was dissolved in dichloromethane (40 mL). While the solution was chilled in a dry ice/acetone bath, triethylamine (3.06 mL) was added, followed by dropwise addition of methanesulfonyl chloride (1.70 mL) and stirring for 1 hour. Subsequently, water (40 mL) was added and the mixture was allowed to warm to room temperature. The dichloromethane layer was separated and the aqueous layer was extracted with dichloromethane (40 mL). The dichloromethane layers were combined, washed with water, dried over anhydrous sodium sulfate and concentrated under reduced pressure. The resulting residue was dissolved in N,N-dimethylformamide (120 mL), followed by the addition of tetrabutylammonium cyanide (5.53 g) and sodium cyanide (2.05 g) and stirring at 80° C. for 13 hours. Subsequently, the reaction mixture was concentrated under reduced pressure. Water (50 mL) was then added to the resulting residue and the mixture was extracted with diethyl ether (2×200 mL). The diethyl ether layers were combined, washed with saturated brine, dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (hexane:ethyl acetate=4:1) to give (3R,4S)-1-benzyl-4-methyl-3-pyrrolidinecarbonitrile as a brown oil (3.32 g).

Provenance & Evidence