Water → 3-Pyridinecarbonitrile, 6-(chlorodifluoromethyl)-

Temperature

100 °C

(3E)-1-Chloro-4-ethoxy-1,1-difluorobut-3-en-2-one (7.36 g, 40 mmol) was dissolved in dry toluene (40 mL) and treated with 3-dimethylaminoacrylonitrile (4.61 g, 48 mmol) at room temperature. The solution was heated at about 100° C. for 3.5 hr. The solvent was then removed under reduced pressure and the remaining mixture was re-dissolved in DMF (20 mL), treated with ammonium acetate (4.62 g, 60 mmol) and stirred at room temperature overnight. Water was added to the reaction mixture and the resulting mixture was extracted with ether-CH2CH2 (1:2, v/v) twice. The combined organic layer was washed with brine, dried, filtered and concentrated. The residue was purified on silica gel to give 3.1 g of 6-[chloro(difluoro)methyl]nicotinonitrile (A) as light colored oil in 41% yield. GC-MS: mass calcd for C7H3ClF2N2 [M]+ 188. Found 188.

1. customThe solvent was then removed under reduced pressure
2. dissolutionthe remaining mixture was re-dissolved in DMF (20 mL)
3. extractionthe resulting mixture was extracted with ether-CH2CH2 (1:2
4. washThe combined organic layer was washed with brine
5. customdried
6. filtrationfiltered
7. concentrationconcentrated
8. customThe residue was purified on silica gel

ORD record

ord-df96c01abb2f455b9a6e9d981eb3711f

Source dataset

uspto-grants-2014_03

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08669278B2