Water → rel-(3R,3aR,5R)-5-cyclopropyl-3-(methoxymethyl)-3,3a,4,5-tetrahydro-7H-pyrano[3,4-c][1,2]oxazole

Temperature

0 °C

Sodium hydride (60% in oil, 395 mg, 9.88 mmol) was slurried in N,N-dimethylformamide (30 mL) and cooled in an ice bath. A solution of rel-[(3R,3aR,5R)-5-cyclopropyl-3,3a,4,5-tetrahydro-7H-pyrano[3,4-c][1,2]oxazol-3-yl]methanol (C37) (1.30 g, 6.59 mmol) in minimal N,N-dimethylformamide was added drop-wise, and the reaction mixture was stirred at 0° C. for 30 minutes. Iodomethane (0.45 mL, 7.2 mmol) was then added in a drop-wise manner, and the reaction was allowed to proceed for an additional 30 minutes at 0° C. Water was added, and the mixture was warmed to room temperature and extracted twice with ethyl acetate. The combined organic layers were washed with saturated aqueous sodium chloride solution, dried over sodium sulfate, filtered, and concentrated in vacuo. Chromatography on silica gel (Gradient: 0% to 60% ethyl acetate in heptane) provided the product as an oil. Yield: 1.0 g, 4.7 mmol, 71%. LCMS m/z 212.1 [M+H+].

1. temperaturecooled in an ice bath
2. waitto proceed for an additional 30 minutes at 0° C
3. temperaturethe mixture was warmed to room temperature
4. extractionextracted twice with ethyl acetate
5. washThe combined organic layers were washed with saturated aqueous sodium chloride solution
6. dry with materialdried over sodium sulfate
7. filtrationfiltered
8. concentrationconcentrated in vacuo

ORD record

ord-5f73866bb70940a0a9f76d65461e00ab

Source dataset

uspto-grants-2016_08

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09403846B2