Diethyl cyanophosphonate → 3-cyano-N-methoxy-N-methyl-5-(trifluoromethyl)benzamide

To a solution of 3-cyano-5-(trifluoromethyl)benzoic acid (200 mg, 0.93 mmol) in tetrahydrofuran (2 mL) stirred on an ice bath was added N,O-dimethylhydroxyamine hydrochloride (145 mg, 1.49 mmol), N,N-diisopropylethylamine (470 mg, 3.64 mmol) and diethyl cyanophosphate (DEPC, 227 mg, 1.39 mmol), and the mixture was stirred at room temperature for 1 hour. The reaction mixture was concentrated under reduced pressure, and the resulting residue was added with 1 M hydrochloric acid (0.5 mL), and extracted with ethyl acetate. The organic layer was washed with saturated brine, then dried anhydrous sodium sulfate, and concentrated under reduced pressure, and the resulting residue was purified by silica gel column chromatography (hexane:ethyl acetate=3:1) to obtain 3-cyano-N-methoxy-N-methyl-5-(trifluoromethyl)benzamide (196 mg, 82%) as a pale yellow solid.

1. concentrationThe reaction mixture was concentrated under reduced pressure
2. additionthe resulting residue was added with 1 M hydrochloric acid (0.5 mL)
3. extractionextracted with ethyl acetate
4. washThe organic layer was washed with saturated brine
5. concentrationdried anhydrous sodium sulfate, and concentrated under reduced pressure
6. customthe resulting residue was purified by silica gel column chromatography (hexane:ethyl acetate=3:1)

ORD record

ord-b615c361c869473783e9aef62c0396ee

Source dataset

uspto-grants-2010_02

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07659271B2