Imidazole → tert-Butyl (3S)-3-(iodomethyl)pyrrolidine-1-carboxylate

Participants

Reaction Steps

Triphenylphosphine (182.2 g, 695 mmol) and imidazole (47.4 g, 696 mmol) were dissolved in dichloromethane (1.6 L), and iodine (70.4 g, 555 mmol) was then added to the above obtained solution under ice-cold condition. The obtained mixture was stirred for 10 minutes. After that, a dichloromethane solution (200 mL) of the (S)-tert-butyl 3-(hydroxymethyl)pyrrolidine-1-carboxylate (55.8 g, 278 mmol) synthesized by a method described in the known method (Bioorg. Med. Chem. Lett., 19, 2829-2834 (2009)) was further added to the reaction solution, and the obtained mixture was then stirred at room temperature for 15 hours. Thereafter, the reaction solution was washed with an aqueous solution of sodium sulfite, was then dried over anhydrous sodium sulfate, and was then concentrated in vacuo. The obtained residue was purified by silica gel chromatography (hexane/ethyl acetate=2%→25%) to obtain (S)-tert-butyl 3-(iodomethyl)pyrrolidine-1-carboxylate (73.2 g, 85%) in the form of a colorless oily product.

Provenance & Evidence