Dimethylformamide → methyl 3,5-difluoro-4-formylbenzoate

To a solution of methyl 3,5-difluorobenzoate (1 gm, 5.8 mmol) in dry tetrahydrofuran (20 mL), lithium diisopropylamide (0.621 gm, 5.8 mmol, 15% solution in tetrahydrofuran and heptane) was added at −78° C. The resulting reaction mixture was stirred for about 1 hour. Dimethylformamide (0.51 g, 6.9 mmol) was added drop wise to the reaction mixture and stirring was continued for about 3 hours at −78° C. The reaction was warm up to room temperature. Saturated aqueous ammonium chloride solution (20 mL) was added to quench the reaction mass. The aqueous phase was extracted with ethyl acetate (3×50 mL) and the combined organic layer dried over anhydrous sodium sulfate, filtered and concentrated. The crude product was purified by column chromatography over silica gel (100-200) using ethyl acetate/hexane gradient elution to afford methyl 3,5-difluoro-4-formylbenzoate (0.5 gm, 31.25%).

1. customThe resulting reaction mixture
2. stirringstirring
3. waitwas continued for about 3 hours at −78° C
4. customto quench the reaction mass
5. extractionThe aqueous phase was extracted with ethyl acetate (3×50 mL)
6. dry with materialthe combined organic layer dried over anhydrous sodium sulfate
7. filtrationfiltered
8. concentrationconcentrated
9. customThe crude product was purified by column chromatography over silica gel (100-200)
10. washethyl acetate/hexane gradient elution

ORD record

ord-5143de6160894de8b7a37bbee6c968d8

Source dataset

uspto-grants-2016_06

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09364466B2