Process for producing 4,4,4-trifluoro-3-hydroxybutyric acid derivatives

A process for increasing optical purity of an optically active 4,4,4-trifluoro-3-hydroxy-1-aryl-1-butanone derivative represented by the formula [1], said process comprising the sequential steps of:

• (a) dissolving said derivative in ethyl acetate with heating to prepare a solution;
• (b) allowing said solution to stand still in an open system to evaporate the ethyl acetate, thereby obtaining a product in which racemic crystals of said derivative are precipitated;
• and
• (c) removing said racemic crystals from the product of the step (b), thereby obtaining said derivative that has an optical purity higher than that of said derivative of the step (a),
• wherein X is a hydrogen, a C1-6 alkyl, a C1-6 alkoxy, or a halogen atom selected from the group consisting of F, C1, Br and I;
• and the symbol * represents an asymmetric carbon.

A process for increasing optical purity of an optically active 4,4,4-trifluoro-3-hydroxy-1-aryl-1-butanone derivative represented by the formula [1], said process comprising the steps of:

• (a) dissolving said derivative, which has a first optical purity of 90% ee or greater, in n-hexane to prepare a solution;
• and
• (b) adding optically pure seed crystals of said derivative to said solution, said optically pure seed crystals having an optical purity of 99% ee or greater, thereby recrystallizing said derivative from said solution in a form of crystals having a second optical purity that is higher than said first optical purity,
• where X is a hydrogen, a C1-6 alkyl, a C1-6 alkoxy, or a halogen atom selected from the group consisting of F, Cl, Br and I;
• and the symbol * represents an asymmetric carbon.

A process for increasing optical purity of an optically active 4,4,4-trifluoro-3-hydroxy-1-aryl-1-butanone derivative represented by the formula [1], said process comprising the sequential steps of:

• (a) dissolving said derivative, which has a first optical purity less than 90% ee, in a recrystallization solvent that is n-hexane or a mixture of toluene and n-heptane under heating to prepare a first solution, said recrystallization solvent being in an amount of from 5 ml to 50 ml per gram of said derivative;
• (b) allowing said first solution to stand still at a temperature within a range of from room temperature to −15° C., thereby precipitating racemic crystals of said derivative, from said first solution;
• (c) removing said racemic crystals from said first solution obtained by the step (b), thereby obtaining a second solution in which said derivative having a second optical purity of 90% ee or higher is dissolved;
• and
• (d) adding optically pure seed crystals of said derivative to said second solution, said seed crystals having an optical purity of 99% ee or greater, thereby recrystallizing said derivative from said second solution in a form of crystals having a third optical purity that is higher than said second optical purity,
• where X is a hydrogen, a C1-6 alkyl, a C1-6 alkoxy, or a halogen atom selected from the group consisting of F, Cl, Br and I;
• and the symbol * represents an asymmetric carbon,
• wherein, when said recrystallization solvent of the step (a) is the mixture of toluene and n-heptane, a relative proportion of said toluene to said n-heptane is in a range of from 1:10 to 1:6.

A process for increasing optical purity of an optically active 4,4,4-trifluoro-3-hydroxybutanic aryl ester derivative represented by the formula [1], said process comprising the sequential steps of:

• (a) dissolving said derivative, which has a first optical purity, in a recrystallization solvent that is n-hexane or a mixture of n-hexane and toluene with heating to prepare a solution, said recrystallization solvent being in an amount of from 5 ml to 40 ml per gram of said derivative;
• and
• (b) allowing said solution to stand still at room temperature, thereby recrystallizing said derivative from said solution in a form of crystals having a second optical purity that is higher that said first optical purity,
• where X is a hydrogen, a C1-6 alkyl, a C1-6 alkoxy, or a halogen atom selected from the group consisting of F, Cl, Br, and I;
• and the symbol * represents an asymmetric carbon,
• wherein, when said recrystallization solvent of the step (a) is the mixture of n-hexane and toluene, a relative proportion of said n-hexane to said toluene is in a range of from 1:1 to 10:1.

A process for increasing optical purity of an optically active compound represented by the Formula,

• wherein X is a hydrogen, a C1-6 alkyl, a C1-6 alkoxy, or a halogen atom selected from the group consisting of F, Cl, Br and I;
• and the symbol * represents an asymmetric carbon, said process comprising the sequential steps of:
• (a) dissolving same compound, which has a first optical purity, in a recrystallization solvent that is n-hexane with heating to prepare a solution, said recrystallization solvent being in an amount of about 40 ml per gram of said compound;
• and
• (b) allowing said solution to stand still at room temperature in the presence of seed crystals of said compound, thereby recrystallizing said compound from said solution in a form of crystals having a second optical purity that is higher than said first optical purity.