4-Methylmorpholine → 2-(4-cyclohexyloxy-phenyl)-N-methoxy-N-methyl-acetamide

To a stirred solution of (4-cyclohexyloxy-phenyl)-acetic acid (181 mmol, 42.4 g) in anhydrous DCM (200 mL) at 0° C. was added oxalyl chloride (362 mmol, 36.6 mL) and continued stirring for 12 h during which time the reaction mixture slowly attained room temperature. The reaction mixture was concentrated in vacuo to remove volatile impurities and dried under high vacuum. To a stirred solution of N,O-dimethylhydroxylamine hydrochloride (226 mmol, 22.1 g) and N-methylmorpholine (407 mmol, 44.8 mL) in anhydrous DCM (200 mL) at 0° C. was added the acid chloride obtained above, dissolved in DCM (50 mL) dropwise. The reaction mixture was stirred for 12 h allowing it to slowly attain room temperature. The reaction mixture was washed with water (2×200 mL), brine (100 mL), dried (Na2SO4), filtered, and concentrated under reduced pressure. The residue was purified on a 330 g SiO2 cartridge with 20-30% ethyl acetate in hexanes to provide 2-(4-cyclohexyloxy-phenyl)-N-methoxy-N-methyl-acetamide.

1. concentrationThe reaction mixture was concentrated in vacuo
2. customto remove volatile impurities
3. customdried under high vacuum
4. customobtained above,
5. stirringThe reaction mixture was stirred for 12 h
6. customto slowly attain room temperature
7. washThe reaction mixture was washed with water (2×200 mL), brine (100 mL)
8. dry with materialdried (Na2SO4)
9. filtrationfiltered
10. concentrationconcentrated under reduced pressure
11. customThe residue was purified on a 330 g SiO2 cartridge with 20-30% ethyl acetate in hexanes

ORD record

ord-447fdbee4ce44db9bcbc89e638362257

Source dataset

uspto-grants-2014_06

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08741900B2