Cyclohexane → (S)-N-(Methylsulfonyl)-2-oxo-3-[[(phenylmethoxy)-carbonyl]amino]-1-azetidinecarboxamide

Participants

Reaction Conditions

Reaction Steps

A stirred suspension of (S)-(2-oxo-3-azetidinyl)carbamic acid, phenylmethyl ester (2.20 g; see example 1C) in 60 ml of dry tetrahydrofuran under nitrogen was warmed using a water bath at 40° C. until solution occurs. The solution was cooled to -75° C., and 7.4 ml of 1.35 M sec-butyl lithium in cyclohexane (10 mmol) was added. After stirring for 2 minutes, (methylsulfonyl) isocyanate (about 1.20 g) was added. This reaction was stirred at -75° C. for 10 minutes and poured into 100 ml of 0.5 M pH 5.5 monobasic potassium phosphate buffer. Ethyl acetate was added, and the pH was adjusted to 7. After several extractions with ethyl acetate, the aqueous layer was covered with ethyl acetate and adjusted to pH 2. Repeated extraction with ethyl acetate gave an acidic extract, which was dried (sodium sulfate) and evaporated to a residue (2.61 g). Chromatography of this residue on 250 g of silicAR CC-4 using dichloromethane and then 1% methanol in dichloromethane provided 1.82 g of product as a residue.

Provenance & Evidence