p-Toluenesulfonic acid → 1-[[(3S)-3-(Benzoylamino)-2-oxo-1-azetidinyl]carbonyl]-L-proline

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Reaction Conditions

Reaction Steps

A solution of (S)-1-[[3-[[(phenylmethoxy)carbonyl]amino]-2-oxo-1-azetidinyl]carbonyl]-L-proline, phenylmethyl ester (0.35 g, 0.78 mmole; prepared as described in examples 22 and 23) in 4.5 ml of dimethylformamide with 0.15 g (0.8 mmole) of p-toluenesulfonic acid and 0.2 g of 10% palladium on charcoal was hydrogenated at 1 atmosphere and 25° C. for 3 hours. The solution was chilled to 0° C. and treated with 0.3 g (2.3 mmoles) of diisopropylethylamine followed by 0.16 g (1.1 mmole) of benzoyl chloride, and stirred at 5° C. for 31/2 days. Water (10 ml) was added to the dimethylformamide solution and the slurry filtered on Celite. The pH was 3.35, and this was adjusted to 2.0 with dilute hydrochloric acid. The solution was extracted with ethyl acetate, saturated with solid sodium chloride and extracted again. The organics were dried (sodium sulfate) and evaporated to a yellow oil which showed one major component by TLC (Rf=0.56) with some less polar impurities. The oil was dissolved in dichloromethane and diluted to cloud with hexane. Scratching gave 70 mg of a white solid, melting point 148°-151° C.

Provenance & Evidence