Chloromethyl Methyl Ether → HCID 67406604, compound

Temperature

-78 °C

To a solution of lithium diisopropylamide (110 mmol, 100 ml of THF, prepared from diisopropylamine (15.6 ml, 110 mmol) and n-butyl lithium (70.1 ml, 1.57M, 110 mmol)) was added (2R,5S)-2-phenyl-3-oxa-1-azabicyclo(3.3.0)octan-8-one (10.2 g, 50 mmol) under stirring at −78° C. After stirring at the same temperature for 1 hour, a solution of chloromethyl methyl ether (5.7 ml, 75 mmol) in THF (50 ml) was added to the reaction mixture and stirring was conducted further at −78° C. for 90 minutes. The reaction mixture was poured in a saturated aqueous solution of ammonium chloride, followed by extraction with ethyl acetate. The extract was washed with saturated brine, dried over anhydrous magnesium sulfate and distilled under reduced pressure to remove the solvent. The residue was purified by silica gel column chromatography (middle pressure Yamazen, linear gradient of n-hexane/ethyl acetate from 9:1 to 7:3, 30 ml/min, φ 80 mm×300 mm, range 0.08) to give (2R,5S,7S)-7-methoxymethyl-2-phenyl-3-oxa-1-azabicyclo(3.3.0)octan-8-one (1.06 g, 9%) as a colorless oil.

1. stirringAfter stirring at the same temperature for 1 hour
2. stirringstirring
3. extractionfollowed by extraction with ethyl acetate
4. washThe extract was washed with saturated brine
5. dry with materialdried over anhydrous magnesium sulfate
6. distillationdistilled under reduced pressure
7. customto remove the solvent
8. customThe residue was purified by silica gel column chromatography (middle pressure Yamazen, linear gradient of n-hexane/ethyl acetate from 9:1 to 7:3, 30 ml/min, φ 80 mm×300 mm, range 0.08)

ORD record

ord-a2572f1994054c8e80dfd190a984f9a0

Source dataset

uspto-grants-2007_01

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07157487B2