2,6-Lutidine → 2,2-Difluoro-N-methoxy-N-methylacetamide

Participants

Reaction Conditions

Reaction Steps

A solution of difluoroacetic acid (4.1 g, 42.7 mmol) in dry dichloromethane (80 ml), under N2, was treated with oxalyl chloride (5.69 g, 44.8 mmol). After stirring at 35° C. for 3 h, the reaction was cooled to 0° C. and treated with N,O-dimethylhydroxylamine hydrochloride (5.0 g, 51.2 mmol), then cooled to -20° C., and treated dropwise with 2,6-dimethylpyridine (19.86 ml, 171 mmol). The reaction was allowed to warm up to room temperature over 2 h then quenched by the addition of ice and water. Orthophosphoric acid (2M) was added until the aqueous layer reached pH4. The aqueous and organic phases were separated and the organic layer was washed with 2M orthophosphoric acid (2×50 ml). The organic layer was dried (Na2SO4) then concentrated in vacuo and the residue was distilled to afford the title compound (D5) as a clear oil (3.72 g, 63%) b.p. 60° C. at 1.5 mm Hg (Kugelrohr).

Provenance & Evidence