Triethylamine → tert-butyl (2S)-2-[(methanesulfonyloxy)methyl]pyrrolidine-1-carboxylate

Participants

Reaction Steps

A solution of 2-(S)-hydroxymethyl-pyrrolidine-1-carboxylic acid tert-butyl ester (compound (2) obtained from above, 109 g, 99.5 g for 100% yield, 0.49 mol) in dichloromethane (500 mL) was cooled to 0° C. Triethylamine (139 mL, 101 g, 1 mol) was added to the cold solution dropwise while maintaining the reaction temperature below 0° C. Methanesulfonyl chloride (58 mL, 85.8 g, 0.75 mol) was added dropwise to reaction mixture while maintaining the reaction temperature at below 0° C. (˜1 hour). The reaction mixture was stirred at room temperature overnight (˜11 hours). HPLC showed absence of starting material. The reaction mixture was quenched with 1 M H3PO4 (300 mL) and mixed for 15 minutes. The organic layer was separated and washed with 1 M aqueous H3PO4 (2×300 mL), followed by saturated aqueous NaHCO3 (4×250 mL), dried over MgSO4, filtered, and concentrated to leave an oily residual product (132 g, 95.6% yield). 1H NMR (CDCl3):δ 1.48 (s, 9H, 3×CH3), 1.82–2.08 (m, 4H, 2×CH2), 3.01 (s, 3H, CH3), 3.36 (m, 2H, CH2), 3.944.18 (m, 2H, CH2) and 4.29 (m, 1H CH); [M+H]+ at m/z 280.

Provenance & Evidence