4-Methylmorpholine → benzhydryl (6R,7R)-7-[[(2Z)-2-methoxyimino-2-[2-[(2-methylpropan-2-yl)oxycarbonylamino]-1,3-thiazol-4-yl]acetyl]amino]-3-methylsulfonyloxy-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylate

Participants

Reaction Steps

To a suspension of 7β-amino-3-methanesulfonyloxy-3-cephem-4-carboxylic acid diphenylmethyl ester hydrochloride (994 mg: 2 mMol.) and (Z)-2-(2-t-butoxycarbonylaminothiazol-4-yl)-2-methoxyiminoacetic acid (662 mg: 2.2 mMol.) in dichloromethane (16 ml) is added at -30° C. N-methylmorpholine (0.72 ml: 6.6 mMol.) and phenyl dichlorophosphate (0.33 ml: 2.2 mMol.), and the mixture is stirred at the same temperature for 2.5 hours. The reaction mixture is quenched by adding 10% hydrochloric acid (5 ml) and extracted with ethyl acetate. The extract is washed with water, 5% aqueous sodium hydrogen carbonate, and water, dried over sodium sulfate, and concentrated. The residue is purified by silica gel chromatography (toluene: ethyl acetate=2:1 containing 0.5% of acetic acid) to give 7β-[(Z)-2-(2-t-butoxycarbonylaminothiazol-4-yl)-2-methoxyiminoacetyl]amino-3-methanesulfonyloxy-3-cephem-4-carboxylic acid diphenylmethyl ester (1.07 g). Yield: 72%.

Provenance & Evidence