Potassium Cyanide → Tert-butyl 3-cyano-3-fluoropyrrolidine-1-carboxylate

Participants

Reaction Conditions

Reaction Steps

To a solution of tert-butyl 3-oxopyrrolidine-1-carboxylate (2.0 g, 10.8 mmol) in THF (10 mL) at 0° C. was added KCN (1.05 g, 16.2 mmol) followed by H2O (10 mL). To the homogeneous orange-brown reaction mixture was added a solution of sodium bisulfite (1.69 g, 16.2 mmol) in H2O (10 mL). The cloudy reaction mixture was stirred at 0° C. for 1 h then extracted with CHCl3 (3×). The combined organic layers were dried over MgSO4 and concentrated. The resultant light brown oil was dissolved in CH2Cl2 (30 mL) and cooled to −78° C. then DAST (90%) (1.74 ml, 11.9 mmol) was slowly added. The reaction mixture was stirred at −78° C. for 10 min then warmed to 0° C. and stirred for 1 h. Carefully quenched with saturated aqueous NaHCO3 then diluted with H2O and extracted with CH2Cl2. The combined organics were dried over MgSO4 and concentrated to a brown oil which was purified by SiO2 chromatography (10% to 25% EtOAc/hexanes) to afford 0.45 g (20%) of tert-butyl 3-cyano-3-fluoropyrrolidine-1-carboxylate as a white solid.

Provenance & Evidence