Lithium iodide → (S)-2-Iodomethyl-pyrrolidine-1-carboxylic acid tert-butyl ester

Participants

Reaction Conditions

Reaction Steps

A solution of 2-(S)-methanesulfonyloxymethyl-pyrrolidine-1-carboxylic acid tert-butyl ester (compound (3) obtained from above, 30 g, 0.10 mol) in anhydrous tetrahydrofuran (600 mL) was cooled to 0° C. Lithium iodide (144 g, 1 mol) was added to the cold reaction mixture as a solid in portions while maintaining the reaction temperature at below 30° C. The reaction mixture was warmed to 62° C. until HPLC showed less than 2% starting material. The reaction mixture was quenched with 10% aqueous sodium thiosulfate (300 mL). Ethyl acetate (600 mL) was added to reaction mixture. The organic layer was separated. The aqueous layer was re-extracted with ethyl acetate (3×50 mL). The combined organic layer was washed with brine (2×100 mL), dried over MgSO4, filtered, and concentrated to leave an oily residual product (26.3 g, 78.6% yield). 1H NMR (CDCl3): δ 1.46 (d, 3H, CH3), 1.48 (d, 6H, 2×CH3), 1.792.14 (m, 4H, 2×CH2), 3.14–3.52 (m, 4H, 2×CH2) and 3.88 (m, 1H, CH); [M+H]+ at m/z 312.

Provenance & Evidence