RENGA Dzhejms M. (US),РЕНГА Джеймс М. (US),UAJTEKER Gregori T. (US),УАЙТЕКЕР Грегори Т. (US),DZHONSON Piter Li (US),ДЖОНСОН Питер Ли (US),GELLIFORD Kristofer (US),ГЭЛЛИФОРД Кристофер (US),RENGA Dzhejms M.,РЕНГА Джеймс М.,UAJTEKER Gregori T.,УАЙТЕКЕР Грегори Т.,DZHONSON Piter Li,ДЖОНСОН Питер Ли,GELLIFORD Kristofer,ГЭЛЛИФОРД Кристофер
申请号：
RU2015127993
公开号：
RU0002653855C2
申请日:
2013.12.12
申请国别(地区):
RU
年份:
2018
代理人:
摘要：
FIELD: chemistry.SUBSTANCE: invention relates to a process for the preparation of 4-amino-5-fluoro-3-chloro-6-(substituted)picolinate of formula I, comprising steps of a) contacting trifluoroacetic acid with p-methoxyaniline in the presence of triarylphosphine and a trialkylamine base in a carbon tetrachloride solvent to form acetimidoyl chloride of formula A； b) contacting the acetimidoyl chloride of formula A with 3,3-dialkoxyprop-1-yne of formula B in the presence of copper (I) iodide, an alkali metal iodide and an alkali metal phosphate in a polar aprotic solvent to obtain (imino)pent-2-ynedialkylacetal of formula C； c) cyclisation of (imino)pent-2-ynedialkyl acetal of formula C with amine R1-CH2-NH2 in the presence of an inorganic base of an alkali metal in a polar aprotic solvent at a temperature from about room temperature to about 100°C to form 4-(4-methoxyphenyl)amino-5-fluoro-6-(substituted)pyridine-2-dialkyl acetal of formula E； d) chlorination of 4-(4-methoxyphenyl)amino-5-fluoro-6-(substituted)pyridine-2-dialkylacetal of formula E with 1,3-dichloro-5,5-dimethylimidazolidine-2,4-dione of formula F in a polar solvent to obtain protected 4-amino-5-fluoro-3-chloro-6-(substituted)pyridine-2-dialkylacetal of formula G； e) removing the protection and hydrolysis of the protected 4-amino-5-fluoro-3-chloro-6-(substituted)pyridine-2-dialkylacetal of formula G with the aid of a mineral acid in a polar solvent to obtain 4-amino-5-fluoro-3-chloro-6-(substituted)picolinaldehyde of formula H； f) oxidising 4-amino-5-fluoro-3-chloro-6-(substituted)picolinaldehyde of formula H with an alkali metal chloride in the presence of an inorganic acid and a hypochlorous acid acceptor in an aqueous alcoholic solvent to obtain 4-amino-5-fluoro-3-chloro-6-(substituted)picolinic acid of formula J and g) esterifying 4-amino-5-fluoro-3-chloro-6-(substituted)picolinic acid of formula J with a compound of formula R2X, in which X is OH, Cl, Br or I, to obtain 4-amino-5-fluoro-3-chloro-6-(s
