METHOD FOR PRODUCING S-9-FLUORO-7-OXO-2,3-DIHYDRO-7H- PYRIDO(1,2,3-DE)(1,4) BENZOXAZINE-6-CARBOXYLIC ACID

摘要

PURPOSE: A method for producing S-9-fluoro-7-oxo-2,3-dihydro-7H- pyrido(1,2,3-de)(1,4) benzoxazine-6-carboxylic acid is provided, thereby the titled compound can be simply produced with low costs. CONSTITUTION: The method for producing S-9-fluoro-7-oxo-2,3-dihydro-7H- pyrido(1,2,3-de)(1,4) benzoxazine-6-carboxylic acid of the formula (1) as quinolon antimicrobial agent comprises the steps of: reacting 2,3,4-trifluoroaniline with (S)-(-)-2-alkyl or allyl substituted propionic acid ethylester, or (S)-(-)-2-alkyl or allyl substituted propionic acid group in the presence of base to produce (S)-(-)-2-(2,3,4-trifluoroanilino)propionic acid; reducing (S)-(-)-2-(2,3,4-trifluoroanilino)propionic acid with the reducing agent in the presence of or absence of acid catalysts under metal complex or organic complex to produce (S)-(+)-N-(3-hydroxy-2-propyl)- 2,3,4-trifluoroaniline; reacting (S)-(+)-N- (3-hydroxy-2-propyl)- 2,3,4-trifluoroaniline with diethyl ethoxy methylene malonate to produce (S)-(-)-ethyl-9,10- difluoro-3-methyl-7-oxo-2,3- dihydro-7H-pyrido(1,2,3-de) (1,4) benzooxazine-6-carboxylate; hydrolyzing (S)-(-)-ethyl- 9,10- difluoro-3-methyl- 7-oxo-2,3- dihydro-7H-pyrido (1,2,3-de) (1,4) benzooxazine-6-carboxylate with inorganic acid to produce (S)-(-)-9,10- difluoro-3-methyl- 7-oxo-2,3- dihydro-7H-pyrido (1,2,3-de) (1,4) benzooxazine-6- carboxylic acid; and reacting (S)-(-)-9,10- difluoro-3-methyl- 7-oxo-2,3- dihydro-7H-pyrido (1,2,3-de) (1,4) benzooxazine-6- carboxylic acid with N-methylpiperazine, tertiary ammonium salt, and iodine to produce S-9-fluoro-7-oxo-2,3-dihydro-7H- pyrido(1,2,3-de)(1,4) benzoxazine-6-carboxylic acid.