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

Temperature

0 °C

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.

1. customThe cloudy reaction mixture
2. extractionthen extracted with CHCl3 (3×)
3. dry with materialThe combined organic layers were dried over MgSO4
4. concentrationconcentrated
5. dissolutionThe resultant light brown oil was dissolved in CH2Cl2 (30 mL)
6. temperaturecooled to −78° C.
7. stirringThe reaction mixture was stirred at −78° C. for 10 min
8. temperaturethen warmed to 0° C.
9. stirringstirred for 1 h
10. customCarefully quenched with saturated aqueous NaHCO3
11. additionthen diluted with H2O
12. extractionextracted with CH2Cl2
13. dry with materialThe combined organics were dried over MgSO4
14. concentrationconcentrated to a brown oil which
15. customwas purified by SiO2 chromatography (10% to 25% EtOAc/hexanes)

ORD record

ord-4aae0eab808449b0a74deb2a4cd1ad92

Source dataset

uspto-grants-2013_08

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08518945B2