RU97114840A

RU97114840A - METHOD FOR SEPARATING CARBINOLES

Info

Publication number: RU97114840A
Application number: RU97114840/04A
Authority: RU
Inventors: Фригола Констанса Хорди; Мария Беррокаль Ромеро Хуана; Роса Куберес Альтисент Мария; Готор Сантамария Висенте
Original assignee: Лабораторьос Дель Др.Эстев, С.А.
Priority date: 1995-12-06
Filing date: 1996-12-04
Publication date: 1999-07-10

Claims

1. The method of obtaining mainly the enantiomer of (R) - (+) - 5- (phenyl) hydroxymethyl-1-methyl-1H pyrazole, denoted by (R) - (+) - 1, isolation from the racemic mixture (±) -5- (phenyl) hydroxymethyl-1-methyl-1H-pyrazole of formula 1, characterized by the sequential implementation of the method, including the use of lipase or its derivative, having enzymatic activity, in the transesterification reaction, as well as hydrolysis of the obtained ester, (5) - (-) - 5- (phenyl) alkylcarbonyloxymethyl-1-methyl 1H-pyrazole, formula 4, wherein R ₁ is methyl or ethyl.

2. The method according to p. 1, characterized in that the lipase or its derivative having enzymatic activity is used as a catalyst in the transesterification reaction between an ester of formula 3, where R ₁ represents methyl or ethyl and R ₂ represents vinyl or isopropenyl, and the enantiomer (S) - (-) - 5- (phenyl) hydroxymethyl-1-methyl-1H-pyrazole, (S) - (-) - 1, which leads to the formation of (S) - (-) - 5- ( phenyl) alkylcarbonyloxymethyl-1-methyl-1H-pyrazole of the formula (S) - (-) - 4, where R ₁ is methyl or ethyl, and recovered without reaction, the enantiomer (R) - (+) - 5- (phenyl) hydroxymet l-1-methyl-1H-pyrazole, (R) - (+) - 1

3. The method according to one of paragraphs. 1 and 2, characterized in that the vinyl acetate of the formula 3, where R ₁ represents methyl and R ₂ represents vinyl, is used as a reagent and as a solvent in the transesterification reaction.

4. The method according to one of paragraphs. 1-3, characterized in that a weakly polar solvent, for example cyclohexane, is used to crystallize the enantiomer of (R) - (+) - 5- (phenyl) hydroxymethyl-1-methyl-1H-pyrazole, (R) - (+) - 1, from a solution also containing an ester of (S) - (-) - 5- (phenyl) methylcarbonyloxymethyl-1-methyl-1H-pyrazole, (S) - (-) - 4, of formula 4, where R ₁ represents methyl.

5. The method according to one of paragraphs. 1 to 3, characterized in that the chromatography is performed on a column of silica gel to separate the carbinol (R) - (+) - 5- (phenyl) hydroxymethyl-1-methyl-1H-pyrazole, (R) - (+) - 1, from an ester of (S) - (-) - 5- (phenyl) methylcarbonyloxymethyl-1-methyl-1H pyrazole of the formula (S) - (-) - 4, where R ₁ is methyl.

6. The method according to one of paragraphs. 1 and 2, characterized in that the hydrolysis of the ester, (S) - (-) - 5- (phenyl) alkylcarbonyloxymethyl-1-methyl-1H pyrazole, of the formula (S) - (-) - 4, where R ₁ represents methyl or ethyl, in an acidic environment, to obtain a racemic mixture of (±) -5- (phenyl) hydroxymethyl-1-methyl-1H-pyrazole of formula 1, which can, in turn, be again subjected to separation by the method corresponding to claims . 1 and 2; the cycle is repeated as many times as needed.

7. The method according to one of paragraphs. 1 and 2, characterized in that the hydrolysis is carried out while maintaining the configuration in the basic medium of the ester (S) - (-) - 5- (phenyl) alkylcarbonyloxymethyl-1-methyl-1H-pyrazole, of the formula (S) - (-) - 4, where R ₁ is methyl or ethyl to obtain (S) - (-) - 5- (phenyl) hydroxymethyl-1-methyl-1H-pyrazole of the formula (S) -1.