Ammonium Chloride → 4,4-Difluoro-N-methoxy-N-methylcyclohexanecarboxamide

Temperature

-70 °C

A mixture of ethyl 4,4-difluorocyclohexane-1-carboxylate (1.9 g, 9.88 mmol) and tetrahydrofuran (60 ml) was cooled to −70° C., and N,O-dimethylhydroxyamine hydrochloride (1.44 g, 14.8 mmol) was added. Further, 1.05 M n-propylmagnesium bromide (24.2 ml, 25.2 mmol) was added dropwise to the reaction mixture at −55° C. over five minutes so that the internal temperature did not exceed −35° C., and the reaction mixture was stirred at 0° C. for 30 minutes. A saturated aqueous ammonium chloride solution was added to the reaction mixture, which was extracted with ethyl acetate. The organic layer was dried over magnesium sulfate, and the solvent was distilled off. The residue was purified by silica gel column chromatography (elution solvent: ethyl acetate/heptane) to give the title compound (1.7 g, yield 83%).

1. customdid not exceed −35° C.
2. extractionwas extracted with ethyl acetate
3. dry with materialThe organic layer was dried over magnesium sulfate
4. distillationthe solvent was distilled off
5. customThe residue was purified by silica gel column chromatography (elution solvent: ethyl acetate/heptane)

ORD record

ord-f251f3024e2946d9af2f5d7addf5eeb1

Source dataset

uspto-grants-2013_07

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08476301B2