Diisopropylamine → Tert-butyl 3-cyano-3-(fluoromethyl)azetidine-1-carboxylate

Participants

Reaction Conditions

Reaction Steps

To an oven-dried 25 mL round bottom flask equipped for stirring was added diisopropylamine (0.659 mL, 4.66 mmol) under nitrogen. THF (5 mL) was added and the colorless solution was cooled to 0° C. To this solution was added n-BuLi (2.92 mL, 4.66 mmol) and the solution was stirred at 0° C. for 30 min. The solution was cooled to −78° C. and a solution of tert-butyl 3-cyanoazetidine-1-carboxylate (0.5 g, 2.74 mmol) in THF (3 mL) was added and the solution was stirred at −78° C. for 30 min. Bromofluoromethane (0.403 g, 3.57 mmol) was added at −78° C. dropwise. The reaction mixture was stirred for 30 min and then allowed to warm to 25° C. and stirred for 16 h. The reaction mixture was quenched at 0° C. with aqueous NH4Cl (5 mL) and extracted with DCM (3×). The extracts were dried over Na2SO4. Purification by silica column chromatography (MeOH/DCM, 0-5%) afforded the title compound as a yellow oil (0.52 g, 94%).

Provenance & Evidence