Sodium Cyanide → 2-(3,3-Difluoro-1-methylcyclobutyl)acetonitrile

Temperature

80 °C

To a solution of Intermediate 229B (200 mg, 0.934 mmol) in DMSO (3 mL) was added NaCN (114 mg, 2.334 mmol) at RT and the reaction mixture was heated to 80° C. and stirred for 12 h. The reaction mixture was cooled to RT, was diluted with water and was extracted with EtOAc (3×10 mL) To the combined organic layer was washed with water and brine, dried over Na2SO4, filtered and the filtrate concentrated under reduced pressure. The residue was purified by silica gel chromatography (12 g REDISEP® column, eluting with 30% EtOAc in petroleum ether). Fractions containing the product were combined and evaporated to afford Intermediate 229C as a brown oil (100 mg, 74%). 1H NMR (400 MHz, DMSO-d6) δ ppm 2.56-2.42 (m, 6H), 1.17 (s, 3H).

1. temperatureThe reaction mixture was cooled to RT
2. extractionwas extracted with EtOAc (3×10 mL) To the combined organic layer
3. washwas washed with water and brine
4. dry with materialdried over Na2SO4
5. filtrationfiltered
6. concentrationthe filtrate concentrated under reduced pressure
7. customThe residue was purified by silica gel chromatography (12 g REDISEP® column, eluting with 30% EtOAc in petroleum ether)
8. additionFractions containing the product
9. customevaporated

ORD record

ord-e1a3c6fa73dc4394912c8d4bcfe5e9e9

Source dataset

uspto-grants-2016_03

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09273058B2