| 简介 |
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-(substituted)picolinate of formula I. Invention also relates to compounds of formulae C, E, G and H. Values of the radicals R1, R2 and R3 are given in the claims. (I), (A), (B), (C), (E), (F), (G), (H), (J).
EFFECT : method makes it possible to prepare 4-amino-5-fluoro-3-chloro-6-(substituted)picolinate from a non-pyridine source.
5 cl, 7 ex |
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