Methyl iodide → Tert-butyl 3-cyano-3-methylpyrrolidine-1-carboxylate

Temperature

-78 °C

To a solution of tert-butyl 3-cyanopyrrolidine-1-carboxylate (1.0 g, 5.1 mmol) in THF (20 mL) at −78° C. was slowly added LiHMDS (1.0 M in THF, 5.6 mL, 5.6 mmol). The reaction mixture was stirred at −78° C. for 30 min then iodomethane (0.48 mL, 7.64 mmol) was slowly added. The reaction mixture was stirred at −78° C. for 30 min then warmed to room temperature and quenched with saturated aqueous NH4Cl. Diluted with H2O and extracted with EtOAc (2×) then dried over MgSO4 and concentrated. The residue was purified by SiO2 chromatography (20% to 40% EtOAc/hexanes) to afford 0.95 g (89%) of tert-butyl 3-cyano-3-methylpyrrolidine-1-carboxylate as a pale yellow solid.

1. customat −78° C.
2. stirringThe reaction mixture was stirred at −78° C. for 30 min
3. temperaturethen warmed to room temperature
4. customquenched with saturated aqueous NH4Cl
5. additionDiluted with H2O
6. extractionextracted with EtOAc (2×)
7. dry with materialthen dried over MgSO4
8. concentrationconcentrated
9. customThe residue was purified by SiO2 chromatography (20% to 40% EtOAc/hexanes)

ORD record

ord-c0ce866b63854928b68cbf5dd69fc246

Source dataset

uspto-grants-2013_08

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08518945B2