Cyclopentanecarbonitrile → (S)-2-methyl-propane-2-sulfinic acid [(R)-1-(1-cyano-cyclopentyl)-ethyl]-amide

Temperature

-78 °C

In a flask, cyclopentanecarbonitrile (3.53 g, 37.1 mmol) was dissolved in THF (40 mL) and cooled at −78° C. LiHMDS (1.0 M in THF, 41 mL, 41 mmol) was added and the mixture stirred for 30 min at −78° C. A solution of (S)-2-methyl-propane-2-sulfinic acid (E)-ethylideneamide (crude from step 1, 1.82 g, 12.4 mmol) in THF (10 mL) was slowly added. The mixture was stirred at −78° C. for 2 h then allowed to warm to room temperature overnight. The reaction mixture was quenched with saturated aqueous ammonium chloride and extracted with EtOAc. The combined organics were washed with brine, dried over MgSO4 and concentrated. The residue was purified by SiO2 chromatography (50-100% EtOAc/heptane) to afford 1.96 g (65%) of (S)-2-methyl-propane-2-sulfinic acid [(R)-1-(1-cyano-cyclopentyl)-ethyl]-amide as a white solid.

1. stirringThe mixture was stirred at −78° C. for 2 h
2. temperatureto warm to room temperature overnight
3. customThe reaction mixture was quenched with saturated aqueous ammonium chloride
4. extractionextracted with EtOAc
5. washThe combined organics were washed with brine
6. dry with materialdried over MgSO4
7. concentrationconcentrated
8. customThe residue was purified by SiO2 chromatography (50-100% EtOAc/heptane)

ORD record

ord-02783ce954fc452685691f8566de287c

Source dataset

uspto-grants-2014_02

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08658646B2