CRYSTALLINE FORM OF y-AMINOBUTYRIC ACID ANALOG
A crystalline form of a γ-aminobutyric acid analog, and methods of preparing same, are provided.
1 .- 8 . (canceled)
9 . A method for preparing crystalline 1-{[(α-isobutanoyloxyethoxy)carbonyl]aminomethyl}-1-cyclohexane acetic acid comprising:
heating 1-{[(α-isobutanoyloxyethoxy)carbonyl]aminomethyl}-1-cyclohexane acetic in a solvent or a solvent mixture to provide a solution; and
cooling the solution to provide crystalline 1-{[(α-isobutanoyloxyethoxy)carbonyl]aminomethyl}-1-cyclohexane acetic acid.
10 . The method of claim 9 , wherein the solvent is selected from the group consisting of methanol, ethanol, 1,2-propane diol, t-butanol, n-butanol, isopropanol, acetic acid, nitromethane, acetonitrile, dimethylsulfoxide, dimethylformamide, N-methyl pyrrolidone, acetone, methyl acetate, ethyl acetate, isopropyl acetate, isobutyl acetate, methyl isobutyl ketone, 1,2-dimethoxyethane, tetrahydrofuran, 2-methyl tetrahydrofuran, toluene, methyl t-butyl ether, chlorobenzene, 1,4-dioxane, diethyl ether, cumene, o-xylene, m-xylene, p-xylene, 2-ethoxyethanol, 1,2-ethandiol, ethyl formate, 2-methoxyethanol, 1-pentanol, anisole, dichloromethane, cis and trans 1,2-dichloroethylene, chloroform, dimethylacetamide, propylacetate and mixtures thereof.
11 . The method of claim 9 , wherein the solvent is a solvent combination comprising a solvent and an anti-solvent.
12 . The method of claim 11 , wherein the anti-solvent is selected from the group consisting of pentane, hexane, heptane, octane, nonane, decane, undecane, dodecane, cis or trans decalin, cyclohexane, methylcyclohexane and mixtures thereof.
13 . The method of claim 12 , wherein the solvent combination comprises ethyl acetate and heptane and the temperature of heating is between about 50° C. and reflux.
14 . The method of claim 13 , wherein the temperature is about 70° C.
15 . The method of claim 13 or 14 , wherein the concentration of 1-{[(α-isobutanoyloxyethoxy)carbonyl]aminomethyl}-1-cyclohexane acetic acid in the ethyl acetate/heptane mixture is between about 0.18 g/mL and about 0.22 g/mL.
16 . The method of claim 11 , wherein the solvent is a solvent combination comprising methyl t-butyl ether and methylcyclohexane and the temperature of heating is in the range of between about 20° C. to about 40° C.
17 . The method of claim 16 , wherein the concentration of 1-{[(α-isobutanoyloxyethoxy)carbonyl]aminomethyl}-1-cyclohexane acetic acid in the solvent combination is between about 0.1 g/mL and about 0.25 g/mL.
18 . The method of claim 17 , wherein the solution is cooled to a temperature between about 0° C. and about 25° C.