Dimethyl Sulfate → (6R, 7R)-2,2-dimethyl-7-(1-methoxy-1-methylethyl)-1-aza-3-oxabicyclo[4.2.0]octan-8-one

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Reaction Steps

To a solution of (6R, 7R)-2,2-dimethyl-7-(1-hydroxy-1-methylethyl)-1-aza-3-oxabicyclo[4.2.0]octan-8-one (43.0 mg) in tetrahydrofuran (1.29 ml) was added dropwise a solution of n-butyl lithium (0.128 ml of 1.74M solution in hexane) at -78° C. After stirring for 10 minutes at the same temperature, hexamethylphosphoric triamide (38.6 μl) was added to the mixture. The resultant solution was stirred for 10 minutes at -78° C. and a solution of dimethylsulfate (38.2 μl) in tetrahydrofuran (0.344 ml) was added to the mixture. The resultant mixture was allowed to warm to ambient temperature over a period of an hour and stirred at ambient temperature overnight. After acetic acid (12.7 μl) was added, the solvent was distilled off, and the residue was dissolved in ethyl acetate (10 ml) and washed with a mixture of 10% aqueous solution of sodium bicarbonate (0.3 ml) and a saturated aqueous sodium chloride (3 ml). The aqueous washings were extracted with ethyl acetate (10 ml) and the combined ethyl acetate extracts were washed with a saturated aqueous sodium chloride. After drying over magnesium sulfate, the ethyl acetate solution was filtered and evaporated in vacuo. The residue was chromatographed on silica gel (2.2 g) eluting with a mixture of ethyl acetate and methylene chloride (1:100 to 1:1) to give (6R, 7R)-2,2-dimethyl-7-(1-methoxy-1-methylethyl)-1-aza-3-oxabicyclo[4.2.0]octan-8-one (24.0 mg) as a white solid.

Provenance & Evidence