4-Toluenesulfonyl chloride → (R)-tert-Butyl 2-((tosyloxy)methyl)pyrrolidine-1-carboxylate

Participants

Reaction Steps

To a well-stirred solution of 2-(R)-hydroxymethyl-pyrrolidine-1-carboxylic acid tert-butyl ester (compound (2), 15 g, 75 mmol) in 42 mL of pyridine and 100 mL of dichloromethane at 0° C. was added a solution of 4toluenesulfonyl chloride (15.68 g, 82.55 mmol) in 75 mL of dichloromethane in a dropwise manner while maintaining the reaction temperature below 0° C. After the addition was complete, the temperature of the reaction was allowed to rise to ambient temperature (˜23° C.) and the reaction was stirred for 5 hours, at which time another 5 grams of 4-toluenesulfonyl chloride was added. The reaction was stirred for 15 hours. The reaction mixture was poured into 150 mL of a 2:1 mixture of dichloromethane and hexane. The mixture was washed twice with a mixture of 100 mL of saturated NaH2PO4 (pH=4.1) solution and water, and then washed with 500 mL of a mixture of 100 mL of Na2HPO4 and water. The organic phase was dried over anhydrous sodium sulfate, concentrated in vacuo, and purified by flash chromatography, eluting with 15% EtOAc in hexane to give a clear oil (22.9 g, 86% yield).

Provenance & Evidence