7-Aminocephalosporanic acid → Cephalosporanic Acid

Participants

Reaction Steps

3-Hydroxy-3,3-diphosphonopropanoic acid, tetramethyl ester is converted to 3-(tert-butoxycarbonyloxy)-3,3-bis(diethoxyphosphono)propionic acid and then to 3-(tert-butoxycarbonyloxy)-3,3-bis(diethoxyphosphono)propanoyl chloride. The acid chloride is then added to α-(Z-methoxyimino)-α-(2-aminothiazol-4-yl)-acetic acid and pyridine to form α-(Z-methoxyimino)-α-{2-[3-(tert-butoxycarbonyloxy)-3,3-bis(diethoxyphosphono)-propanoyl-amino]-thiazol-4-yl}-acetic acid. The latter is reacted with oxaloyl chloride to form the acid chloride, α-(Z-methoxyimino)-α-{2-[3-(tert-butoxycarbonyloxy)-3,3-bis(diethoxyphosphono)-propanoyl-amino)-thiazol-4-yl]-acetyl chloride. This acid chloride is reacted with 7β-amino-3-acetoxymethyl-3-cephem-4-carboxylic acid and pyridine and gives 7β-{α-(Z-methoxyimino)-α-[2-(3-tert-butoxycarbonyloxy)-3,3-bis(diethoxyphosphono)propanoyl-amino)-thiazol-4-yl]-acetamido}-3-acetoxymethyl-3-cephem-4-carboxylic acid. Deprotection with trifluoroacetic acid and anisole yields the title compound.

Provenance & Evidence