Toluene → (S)-1-[[3-[[(Phenylmethoxy)carbonyl]amino]-2-oxo-1-azetidinyl]carbonyl]-D-proline, phenylmethyl ester

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Reaction Conditions

Reaction Steps

To a slurry of dried (S)-3-[[(phenylmethoxy)carbonyl]amino]-2-azetidinone (0.44 g, 2 mmoles) in 10 ml of dry dichloromethane under argon at -10° C. was added triethylamine (0.3 g, 3 mmoles) followed by 4 ml of 12.5% phosgene in toluene (5 mmoles). After stirring for 1.5 hours at -10° C., the solvent was evaporated, and the residue taken up in dichloromethane (10 ml) and chilled to -10° C. To this was added 0.48 g (2 mmoles) of D-proline, phenylmethyl ester, hydrochloride followed by 0.4 g (4 mmoles) of triethylamine. The mixture was stirred at -10° C. for 30 minutes, then quenched and washed with 10% monobasic potassium phosphate. The organics were washed with brine, dried (sodium sulfate), and chromatographed on silica (LPS-1) in 1:1 hexane:ethyl acetate. The pure product fractions (Rf=0.23 on silica, same system) were evaporated to give 0.42 g of a thick oil.

Provenance & Evidence