FIELD: organic chemistry.
SUBSTANCE: inventions are related specifically to a method for obtaining the desired isomer of substituted 2-trifluoromethyl-2H-chromene-3-carboxylic acid. Invention includes a process for preparing the desired isomer of a substituted 2-trifluoromethyl-2H-chromene-3-carboxylic acid, comprising: (a) in a solvent or mixture of solvents, contacting the substituted 2-trifluoromethyl-2H-chromene-3-carboxylic acid with a chiral amine to form salts where the chiral amine is chosen such that the amine salt of the undesired substituted 2-trifluoromethyl-2H-chromene-3-carboxylic acid is greater than the amine salt of the desired substituted 2-trifluoromethyl-2H-chromene-3-carboxylic acid, and ( b) irradiating the mixture with ultraviolet (UV) light, where the irradiation increases the amount of the less soluble chiral amine salt of substituted 2-trifluoromethyl-2H-chromene-3-carboxylic acid in the mixture, where the chiral amine is selected from the group consisting of (S)-N- benzyl-alpha-methylbenzylamine, (1R,2R)-2-amino-1-phenyl-1,3-propanediol, (R)-1-(1-naphthyl)ethylamine, (S)-2-amino-3-phenyl -1-propanol and L-phenylalanine amide, and where the solvent is selected from the group consisting of hexane, heptane, cyclohe xane, toluene, methanol, ethanol, 2-propanol, diisopropyl ether, tert-butyl methyl ether, tetrahydrofuran, 2-methyltetrahydrofuran, dioxane, acetone, methyl ethyl ketone, ethyl acetate, dichloromethane, acetonitrile, N,N-dimethylformamide, N-methylpyrrolidone, dimethyl sulfoxide, water and a mixture of two or more of them, (c) maintaining irradiation for a period of time effective to increase the amount of the desired chiral amine salt of the substituted 2-trifluoromethyl-2H-chromene-3-carboxylic acid isomer, (d) isolating the desired chiral amine salt substituted 2-trifluoromethyl-2H-chromene-3-carboxylic acid from the mixture; and (e) isolating the free form of the desired chiral substituted-2-trifluoromethyl-2H-chromene-3-carboxylic acid from the chiral amine salt by treatment with acid, and where substituted 2 -trifluoromethyl-2H-chromene-3-carboxylic acid is selected from the group consisting of the following compounds: 6-chloro-7-tert-butyl-2-trifluoromethyl-2H-chromene-3-carboxylic acid, 6-chloro-8-methyl-2-trifluoromethyl-2H-chromene-3-carboxylic acid, 6-chloro-8- ethyl 2-trifluoromethyl-2H-chromene-3-carboxylic acid, 6-chloro-5,7-dimethyl-2-trifluoromethyl-2H-chromene-3-carboxylic acid, 6,8-dimethyl-2-trifluoromethyl-2H- chromene-3-carboxylic acid, 6,8-dichloro-2-trifluoromethyl-2H-chromene-3-carboxylic acid, 8-ethyl-6-trifluoromethoxy-2-trifluoromethyl-2H-chromene-3-carboxylic acid, 6-bromo -8-methyl-2-trifluoromethyl-2H-chromene-3-carboxylic acid; and 6-bromo-8-(methyl-D3)-2-trifluoromethyl-2H-chromene-3-carboxylic acid. In addition, an asymmetric transformation method for enriching the desired substituted 2-trifluoromethyl-2H-chromene-3-carboxylic acid isomer is disclosed.
EFFECT: present group of inventions provides efficient production of the desired enantiomer of 2-trifluoromethyl-2H-chromene-3-carboxylic acid in high yield and enantiomeric excess.
18 cl, 6 dwg, 17 tbl, 15 ex
