Dicyclohexylcarbodiimide → tert-butyl 2-methyl-2-[(Z)-[2-oxo-2-[[(3S)-2-oxoazetidin-3-yl]amino]-1-[2-(tritylamino)-1,3-thiazol-4-yl]ethylidene]amino]oxypropanoate

Participants

Reaction Steps

A mixture of 2.20 g (0.01 mmol) of (S)-(2-oxo-3-azetidinyl) carbamic acid phenylmethyl ester, 125 mL of methanol, and 0.68 g of 10% palladium on carbon catalyst was hydrogenated (5 minutes) on a parr apparatus at an initial gauge pressure of 50 psi. After filtration of the catalyst, the solution was concentrated to dryness under reduced pressure. The residual (S)-3-amino-2-azetidinone was dissolved in 10 mL of DMF and added to a mixture of 5.71 g (0.01 mol) of (Z)-α-[[2-(1,1-dimethylethoxy)-1,1-dimethyl-2-oxoethoxy]imino]-2-[(triphenylmethyl)amino]-4-thiazole acetic acid, 40 mL of DMF, 2.06 g (0.01 mol) of N,N'-dicyclohexylcarbodiimide and 1.35 g (0.01 mol) of 1-hydroxybenzotriazole. The mixture was stirred for 4 hours, diluted with 500 mL of water, and adjusted to pH 7.5 with aqueous NaHCO3. The mixture was extracted with four 300 mL portions of ethyl acetate. The combined extracts were washed with water and brine, dried (Na2SO4), decolorized with charcoal, and concentrated to dryness. After purification by HPLC on a Waters Prep 500, using 4:1 ethyl acetate-hexane, 3.8 g of (S,Z)-α-[[2-(1,1-dimethylethoxy)-1,1-dimethyl-2-oxoethoxy]imino]-N-(2-oxo-3-azetidinyl)-2-[(triphenylmethyl)amino]-4-thiazoleacetamide was obtained.

Provenance & Evidence