Acetic Acid → 1-Benzyl-2-methyl-azetidine-2-carboxylic acid ethyl ester

Participants

Reaction Conditions

Reaction Steps

A solution of 2-[benzyl-(2-chloro-ethyl)-amino]-propionic acid ethyl ester (27.4 g, 1 eq.) in 253 mL of dry THF was cooled to −78° C. under argon. KHMDS (15% w/w in toluene, 170.40 g, 1.25 eq.) was slowly added so that temperature was kept below −76° C. The reaction was stirred for 1 h at −76° C., then warmed to 20° C. and stirred for 1 h. Acetic acid (1.74 mL, 0.3 eq.) was added and the reaction was stirred at 20° C. for 10 min. The reaction was quenched with 50 mL of a saturated aqueous solution of NaHCO3 and partially concentrated under reduced pressure. The crude was extracted three times with DCM. The organic layers were dried over MgSO4, filtered and concentrated under reduced pressure. The crude was purified by chromatography on silica gel (elution with heptane/EtOAc 100/0 to 90/10) to afford 1-benzyl-2-methyl-azetidine-2-carboxylic acid ethyl ester (18.75 g, yield=79%).

Provenance & Evidence