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

Temperature

35 °C

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).

1. temperaturethe reaction was cooled to 0° C.
2. temperaturecooled to -20° C.
3. temperatureto warm up to room temperature over 2 h
4. customthen quenched by the addition of ice and water
5. additionOrthophosphoric acid (2M) was added until the aqueous layer
6. customThe aqueous and organic phases were separated
7. washthe organic layer was washed with 2M orthophosphoric acid (2×50 ml)
8. dry with materialThe organic layer was dried (Na2SO4)
9. concentrationthen concentrated in vacuo
10. distillationthe residue was distilled

ORD record

ord-b92aa9a2b3bd46239f135f73f734152f

Source dataset

uspto-grants-1994_05

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US05314901