Patent EA-002039-B1 (EA)
Title: Process for enhancing the optical purity of 2r-[1-hydroxy-1-triflouromethyl-3 cyclopropylpropyn-2yl]-4-chloroaniline
Inventor: CHEN CHENG YI
IPC: C07C215/68
Filed: 1998-09-01
Abstract: 1. A process for enhancing the optical purity of the R-aminoalcohol of formula:   comprising the steps of: (a) adding slowly an acid solution or gas to a solution of the aminoalcohol in an organic solvent to form a slurry of the acid addition salt of the amino alcohol; (b) concentrating the slurry of the amino alcohol acid addition salt of the amino alcohol; (c) flushing the concentrated slurry of the amino alcohol acid addition salt with organic solvent to adjust the solvent composition; (d) aging the slurry of the amino alcohol acid addition salt at ambient temperature for about 2 hours to about 24 hours; (e) filtering the aged slurry of the amino alcohol acid addition salt to isolate a wetcake of the amino alcohol acid addition salt; (f) washing the wetcake of the amino alcohol acid addition salt with cold organic solvent; and (g) drying the wetcake of the amino alcohol acid addition salt to isolate the amino alcohol acid addition salt as a solid with enhanced optical purity. 2. The process as recited in Claim 1, wherein the acid has a pKa of less than or equal to 3. 3. The process as recited in Claim 2, wherein the organic solvent is selected from the group consisting of: isopropyl acetate, ethyl acetate, toluene, methyl t-butyl ether, acetonitrile, tetrahydrofuran, methanol, ethanol, isopropanol, hydrocarbon solvents, and mixtures therefrom. 4. The process as recited in Claim 3, wherein the acid has a pKa of less than or equal to 1. 5. The process as recited in Claim 4, wherein the organic solvent is selected from the group consisting of: isopropyl acetate, ethyl acetate, toluene, methyl t-butyl ether, acetonitrile, tetrahydrofuran, methanol, ethanol, isopropanol, hydrocarbon solvent, and mixtures therefrom. 6. The process as recited in Claim 5, wherein the acid is selected from the group consisting of: HX, where X is defined as halide (Cl, Br, I, or F), H2 SO4, trifluoroacetic acid, trichloroacetic acid, RSO3H, where R represents (C1-C6)-alkyl, (C2-C6)-alkenyl, (C2-C6)-alkynyl, aryl which is defined as phenyl or naphthyl and heteroaryl which is defined as 5 or 6membered ring substituted with one or two heteroatoms selected from O, S, N, and (C1-C6) -alkyl, (C2-C6)-alkenyl, (C2-C6)-alkynyl, aryl or heteroaryl can be substituted or unsubstituted with one, two or three substituents selected from the group consisting of: Br, Cl, F, I, (C1-C6)-alkyl, (C2-C6)-alkenyl, (C2-C6)-alkynyl, (C1-C6)-alkoxy, cyano, nitro, hydroxy, CHO, CO2H, SO3H, CO- C1-C6-alkyl, CO2- C1-C6-alkyl, CONR<1>R<2>, NR<1>R<2>, NR<1>CO- C1-C6-alkyl, wherein R<1> and R<2> are independently defined as: halo (Cl, Br, F, I), CF3, CN, NO2, NH2, NH(C1-C6-alkyl), N(C1-C6-alkyl)2, CONH2, CONH(C1-C6-alkyl), CON(C1-C6-alkyl)2, NHCONH2, NHCONH(C1-C6-alkyl), NHCON(C1-C6- alkyl)2, CO2- C1-C6-alkyl, (C1-C6)-alkyl, (C2-C6)-alkenyl, (C2-C6)-alkynyl, C3-C7-cycloalkyl, or (C1-C6)-alkoxy, such that C1-C6-alkyl is unsubstituted or substituted with aryl, aryl is defined as phenyl or naphthyl, unsubstituted or substituted with C1-C6-alkyl, C1-C6-alkoxy, NO2, or halo (Cl, Br, F, I). 7. The process as recited in Claim 6, wherein the organic solvent is selected from the group consisting of: isopropyl acetate, ethyl acetate, toluene, methyl t-butyl ether, acetonitrile, tetrahydrofuran, methanol, ethanol, isopropanol, and hydrocarbon solvents, and mixtures therefrom. 8. The process as recited in Claim 7, wherein the acid solution or gas is selected from the group consisting of: 1,5 naphthalenedisulfonic acid, ptoluenesulfonic acid, CH3SO3H, triflic acid, and camphorsulfonic acid HCl, HBr, and H2SO4. 9. The process as recited in Claim 8, wherein the acid solution or gas and organic solvent are: HCl and isopropyl acetate, HBr and isopropyl acetate or HBr and a toluene-tetrahydrofuran mixture.