Citric Acid → 3-[(2R)-2-[(3S,4R)-3-[(1R)-1-t-butyldimethylsilyloxyethyl]-2-oxoazetidin-4-yl]propionyl}-spiro[2,3-dihydro-4H-1,3-benzoxazine-2,1'-cyclohexan]-4-one

Participants

Reaction Conditions

Reaction Steps

Under a nitrogen atmosphere, 273 mg (1.0 mmol) of 3-propionyl-spiro[2,3-dihydro-4H-1,3-benzoxazine-2,1′-cyclohexan]-4-one was charged in a 30-ml three-necked flask to dissolve it in 2 ml of tetrahydrofuran. To the resulting solution, 2.44 ml (2.2 mmol) of a tetrahydrofuran solution (0.9M) of n-butylmagnesium chloride was slowly added dropwise at room temperature. The resulting mixture was reacted for 25 minutes under the same conditions. After cooling to 5° C., 2 ml of a tetrahydrofuran solution of 287 mg (1.0 mmol) of (3R,4R)-4-acetoxy-3-[(R)-1-tert-butyldimethylsilyloxyethyl]azetidin-2-one was added at the same temperature. The resulting mixture was stirred for 15 minutes, added with 10 ml of ethyl acetate and then added dropwise with 2 ml of a 10% aqueous solution of citric acid. After separation, the organic layer was washed with 2 ml of a saturated aqueous solution of sodium bicarbonate and 2 ml of a saturated aqueous solution of sodium chloride, dried over anhydrous magnesium sulfate and distilled to remove the solvent. The residue was purified by column chromatography, whereby 263 mg (0.53 mmol) of a condensation product was obtained (yield: 53%, β:α=92:8).

Provenance & Evidence