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

Participants

Reaction Conditions

Reaction Steps

A solution of d,l-proline, benzyl ester (1.13 grams, 5.5 mmol) in 6 ml of dichloromethane was cooled to 0° C. and 1.2 equivalents (0.92 ml) of triethylamine (668 mg, 6.6 mmol) was added. The resulting mixture was immediately added dropwise to a solution of 20% phosgene in toluene (6 ml, 9.9 mmol) at -25° C. After stirring at -25° C. for 1 hour, the volatiles were evaporated without external heating, and the residue was redissolved in 10 ml of dichloromethane and cooled to 0° C. (S)-3-[[(Phenylmethoxy)carbonyl]amino]-2-azetidinone (1.21 grams, 5.5 mmol) and dimethylaminopyridine (67 mg, 0.55 mmol) were added to the stirring solution. Triethylamine (0.92 ml, 6.6 mmol) was added and the reaction mixture was warmed to room temperature and stirred for 24 hours. The reaction mixture was washed with water, dried over anhydrous Na2SO4, filtered and the dichloromethane removed in vacuo. The residue was purified by flash chromatography on silica gel 230-400 mesh (eluting with 40% ethyl acetate in hexane) yielding 1.2 grams of the title compound as a colorless oil.

Provenance & Evidence