Carbon Dioxide → 4-Cyano-2,6-difluorobenzoic acid

Temperature

2.5 °C

To a solution of 3,5-difluorobenzonitrile (3.48 g, 25 mmol, Fluorochem) in THF (35 ml) was added slowly butyl lithium (1.6M in hexanes) (15.63 ml, 25.00 mmol) at −75° C. The resulting solution was stirred for 1 hr at −70-75° C. Then this solution was poured on freshly crushed dry ice CO2 (44.0 g, 1000 mmol). The contents were stirred at room temperature until dry ice disappearance. The solvent was evaporated off under HV. Then residual organic layer was suspended in water and extracted with ethyl acetate (3×50 ml). The product containing aqueous layer was acidified with aqueous HCl solution and the product was re-extracted in the organic layer with Ethylacetate (4×50 ml). The combined organic layers were washed with brine, dried over MgSO4, filtered and evaporated to give a white crystalline solid (2.5731 g, 13.91 mmol, 55.6% yield)

1. customThe solvent was evaporated off under HV
2. extractionextracted with ethyl acetate (3×50 ml)
3. additionThe product containing aqueous layer
4. extractionthe product was re-extracted in the organic layer with Ethylacetate (4×50 ml)
5. washThe combined organic layers were washed with brine
6. dry with materialdried over MgSO4
7. filtrationfiltered
8. customevaporated

ORD record

ord-830c65f007d4438a9490a9cd99f9e041

Source dataset

uspto-grants-2015_06

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09056843B2