Metallation of N-(Pivaloyl)- and N-(tert-Butoxycarbonyl)difluoroanilines: Regiocontrol by Fluorine in the Synthesis of 4-Methoxycarbonyl Derivatives

Article abstract of DOI:10.1055/s-1990-26856

Methyl 2,6-difluoro-4-(pivaloylamino)benzoate (3) and the corresponding 4-(tert-butoxycarbonylamino)-analogue 6 have been synthesised by reacting the appropriate 3,5-difluoroaniline derivatives with butyllithium followed by methyl chloroformate.N-(tert-Butoxycarbonyl)-2,3-difluoroaniline (9) required the "super-basic" butyllithium/potassium tert-butoxide mixture to convert it into methyl 4-(tert-butoxycarbonylamino)-2,3-difluorobenzoate (14): the 2,5-difluoro-analogue was formed in a similar manner.In all cases the regiocontrol of metallation was directed by fluorine rather than by the amide substituent.