Process for the preparation of (6S)-5,6,7,8-tetrahydrofolic acid
AssigneeSapec S.A. fine chemicals
InventorsPascal Jequier, Fabrizio Marazza
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Abstract
(6S)-THF is obtained by adding, in portions, an acid to an aqueous solution of a (6RS)-diastereoisomeric mixture of an alkali metal salt of 5,6,7,8-tetrahydrofolic acid. The addition is made at a temperature from 5.degree. C. to 80.degree. C. for the purpose of the selective crystallization for a period sufficient to stabilize the pH to a value of from 4.8 to 5.3. Then, the formed solid, i.e., (6S)-5,6,7,8-tetrahydrofolic acid, is separated.
Claims10
A process for the preparation of (6S)-5,6,7,8-tetrahydrofolic acid according to formula (I):
- ##STR2## having a diastereoisomeric purity of at least 75%, said process conducted without fractional crystallization of acid addition salts, and comprising a direct crystallization from a (6RS)-diastereoisomeric mixture of an alkali metal salt of 5,6,7,8tetrahydrofolic acid wherein (i) a strong non-oxidizing acid or acetic acid is added in portions over time to an aqueous solution of a (6RS)-diastereoisomeric mixture of an alkali metal salt of 5,6,7,8-tetrahydrofolic acid at a temperature from 5.degree. C. to 80.degree. C. and to an extent effective to adjust and stabilize the pH to a value of from 4.8 to 5.3 to directly and selectively crystallize (6S)-5,6,7,8-tetrahydrofolic acid, and (ii) the formed solid is separated, said solid being (6S)-5,6,7,8-tetrahydrofolic acid having a diastereoisomeric purity of at least 75%.
A process according to 1, wherein the addition of acid and the selective crystallization simultaneously occur and are realized at a temperature from 40.degree. C. to 50.degree. C.
Dependencies are inferred from the claim text.