Acetic Acid → 3,5-Difluoro-4-formylbenzonitrile

To a solution of 3,5-difluorobenzonitrile (1 gm, 7.1 mmol) in dry tetrahydrofuran (20 mL), lithium diisopropylamide (0.769 gm, 7.1 mmol) was added at −78° C. The resulting reaction mixture was stirred for about 1 hour. Dimethylformamide (0.62 g, 8.5 mmol) was added dropwise to the reaction mixture and stirring was continued for about 45 minutes. Acetic acid (1.5 mL) and water (40 mL) were added to the cold solution of reaction mixture. The aqueous phase was extracted with diethyl ether (4×50 mL). The combined organic layer was dried over anhydrous sodium sulfate, filtered and concentrated. The crude product was purified by silica gel (100-200) column chromatography using hexane and ethyl acetate as gradient system to afford pure 3,5-difluoro-4-formylbenzonitrile (0.5 gm, 31.25%).

1. customThe resulting reaction mixture
2. stirringstirring
3. waitwas continued for about 45 minutes
4. extractionThe aqueous phase was extracted with diethyl ether (4×50 mL)
5. dry with materialThe combined organic layer was dried over anhydrous sodium sulfate
6. filtrationfiltered
7. concentrationconcentrated
8. customThe crude product was purified by silica gel (100-200) column chromatography

ORD record

ord-effb54d589a949029c4dbf3b186042e4

Source dataset

uspto-grants-2016_06

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09364466B2