DZHONSON Piter Li,ДЖОНСОН Питер Ли,RENGA Dzhejms M.,РЕНГА Джеймс М.,DZHAMPETRO Natali K.,ДЖАМПЬЕТРО Натали К.,UAJTEKER Gregori T.,УАЙТЕКЕР Грегори Т.,GELLIFORD Kristofer,ГЭЛЛИФОРД Кристофер
申请号：
RU2015127992
公开号：
RU0002658825C2
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-3-halogen-6-(substituted)picolinate of Formula I, which comprises the following steps: (a) contacting difluoroacetic acid or trifluoroacetic acid with tritylamine or tert-butylamine in the presence of triarylphosphine and a trialkylamine base in carbon tetrachloride as a solvent to obtain 2,2-difluoro- or 2,2,2-trifluoro-N-(trityl or t-butyl)ethanimidoyl chloride (Formula A) (b) contacting 2,2-difluoro- or 2,2,2-trifluoro-N-(trityl or isobutyl)ethanimidoyl chloride (Formula A) with 3,3-dialkoxyprop-1-yne (Formula B), where R4 is C1-C4 alkyl, 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-yl of dialkyl acetal of Formula C (c) cyclisation of (imino)pent-2-yne of a dialkyl acetal of Formula C with an amine R1-CH2-NH2 of Formula D, in the presence of an inorganic base of an alkali metal in a polar aprotic solvent at a temperature from about ambient temperature to about 100°C to obtain trityl- or isobutyl-protected 4-amino-6-(substituted)pyridine-2-dialkylacetal of Formula E (d) deprotection and hydrolysis of trityl- or isobutyl-protected 4-amino-6-(substituted)pyridine-2-dialkylacetal of Formula E using a mineral acid in a polar solvent to obtain 4-amino-6-(substituted)picolinaldehyde of Formula F (e) oxidation of 4-amino-6-(substituted)picolinaldehyde of Formula F using an alkali metal chlorite in the presence of an inorganic acid and a hypochlorous acid scavenger in an aqueous alcoholic solvent to obtain 4-amino-6-(substituted)picolinic acid of the Formula G (f) esterification of 4-amino-6-(substituted)picolinic acid of Formula G with a compound of Formula R3Y and (g) halogenating the 4-amino-6- (substituted) picolinate of Formula H with a halogen source to obtain 4-amino-3-halogen-6-(substituted)picolinate of Formula I. X, R, R1, R2 and R3, R4 are given in the claims. Invention relat
