N-METHOXY-N-METHYLTRIFLUOROACETAMIDE

6638-79-5

407-25-0

104863-67-4

To a suspension of N,O-dimethylhydroxylamine hydrochloride (107.2 kg, 1.1 kmol) in dichloromethane (400 L) was sequentially added trifluoroacetic anhydride (210 kg, 1 kmol) and pyridine (174 kg, 2.2 kmol) at 0 °C. The reaction mixture was stirred continuously at 0 °C for 1 hour. Subsequently, the reaction solution was diluted with ice water (300 L) and washed with 2M hydrochloric acid (300 L). The aqueous phase was extracted twice with dichloromethane, the organic phases were combined and dried with anhydrous magnesium sulfate. After concentration of the organic phase, the crude N-methoxy-N-methyl-2,2,2-trifluoroacetamide (Weinreb amide) was obtained with 90% purity and 95% yield, which could be used in the subsequent reaction without further purification.