Preparation of Difluorophosphonoacetic Acid and Its Derivatives

Article abstract of DOI:10.1021/jo00242a034

The preparation of ethyl difluoro(diethoxyphosphinyl)acetate (1) has been effected by the acylation of <(diethoxyphosphinyl)difluoromethyl>zinc bromide with ethyl chloroformate in the presence of a catalytic amount of cuprous bromide.Similarly prepared were ethyl difluoro(diethoxyphosphinyl)pyruvate (2) and N,N-diethyldifluoro(diethoxyphosphinyl)acetamide (3).Bromotrimethylsilane selectively reacted with 1 to yield ethyl difluoroacetate (9).The remaining ethyl carboxylic ester of 9 reacted with iodotrimethylsilane to produce trimethylsilyl difluoroacetate (10), which was subsequently hydrolyzed to yield difluorophosphonoacetic acid (8).The phosphonate 9 was gently chlorinated to yield ethyl difluoro(dichlorophosphinyl)acetate (11).