Hydrazine → HCID 67089002, compound

To a solution of MeCN (1.1 g, 16.8 mmol) in THF (60 mL) was added dropwise n-BuLi in THF (11.2 mL, 40.3 mmol) at −78° C., and the reaction mixture was stirred at −78° C. under N2 for 30 min. Butyl 2,2-difluorocyclopropanecarboxylate (3.0 g, 16.8 mmol) was added at −78° C., and the reaction mixture was allowed to warm to RT over 3 h. The reaction mixture was quenched with water and adjusted to pH 7 with 1N HCl. The mixture was extracted with EtOAc, and the organic layer was washed with brine, dried (Na2SO4), filtered and concentrated in vacuo to afford crude 3-(2,2-difluorocyclopropyl)-3-oxopropanenitrile. A mixture of crude 3-(2,2-difluorocyclopropyl)-3-oxopropanenitrile and hydrazine (2.0 g, 50.4 mmol, 85% pure) in EtOH (30 mL) was stirred at reflux for 16 h. The reaction mixture was concentrated to dryness under reduced pressure. The crude residue was purified by chromatography eluting with an EtOAc/petroleum ether gradient (12.5 to 100% EtOAc) to afford 2.1 g (78.5%) of 45 as a yellow solid: 1H NMR (400 MHz, DMSO-d6): δ 11.40 (br s, 1H), 5.26 (s, 1H), 4.80 (br s, 2H), 2.78-2.66 (m, 1H), 2.04-1.75 (m, 1H), 1.73-1.21 (m, 1H); MS (ESI+) m/z=160.1 [M+1]+.

1. temperatureat reflux for 16 h
2. concentrationThe reaction mixture was concentrated to dryness under reduced pressure
3. customThe crude residue was purified by chromatography
4. washeluting with an EtOAc/petroleum ether gradient (12.5 to 100% EtOAc)

ORD record

ord-e7707ed523484b199adbfcff179cbb6d

Source dataset

uspto-grants-2014_01

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08637537B2