Methanamine, N-methoxy-, hydrochloride (1:1) → HCID 70231221, compound

To a solution of 4,4-difluorocyclohexanecarboxylic acid (5 g, 30.49 mmol) in DCM (40 mL) were added DIPEA (11.8 g, 91.46 mmol) and HATU (17.38 g, 45.73 mmol). The mixture was stirred for 0.5 hr. The N,O-dimethylhydroxylamine hydrochloride (3.56 g, 36.58 mmol) was added to the mixture. The mixture was stirred at 28° C. for 12 hr. Water (20 mL) was added and the mixture was extracted by CH2Cl2 (30 mL*3). The organic layer was washed with brine and dried over sodium sulfate. The organic layer was concentrated to give the crude product, the crude product was purified by column chromatography on silica gel eluted with (petroleum ether/ethyl acetate 10:1→2:1) to gave 4,4-difluoro-N-methyl cyclohexanecarboxamide (4.6 g, 73.36%) for next step.

1. stirringThe mixture was stirred at 28° C. for 12 hr
2. extractionthe mixture was extracted by CH2Cl2 (30 mL*3)
3. washThe organic layer was washed with brine
4. dry with materialdried over sodium sulfate
5. concentrationThe organic layer was concentrated
6. customto give the crude product
7. customthe crude product was purified by column chromatography on silica gel
8. washeluted with (petroleum ether/ethyl acetate 10:1→2:1)

ORD record

ord-6800d4720f8c47caaa37f67bbbb13b94

Source dataset

uspto-grants-2016_06

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09371331B2