Synthesis method of [3aS, 6aR]-1,3-dibenzyl-tetrahydro-4H-fruo [3,4-d]-imidazolyl-2,4 [1H]-diketone [I]

Abstract

The present invention provides the synthesis process of (3aS, 6aR)-1, 3-dibenzyl-tetrahydro-4H-furo[3, 4-d]-imidazolyl-2, 4(1H)-dione. Compound 1, 3-dibenzyl imidazolidine-2-one-2H-furo[3, 4-d]-imidazolyl-2, 4, 6-trione is made to produce enantiotropic selective ring-opening reaction with fatty alcohol and arylkyl alcohol under the catalysis of chiral amine to produce (4S, 5R)-1, 3-dibenzyl-5-alkoxycarbonyl-2-oxyimidazolidine-4-carboxylic acid, which is then reduced with borohydride and ring-closed under Lewis acid catalysis inside organic solvent to produce (3aS, 6aR)-1, 3-dibenzyl-tetrahydro-4H-furo[3, 4-d]-imidazolyl-2, 4(1H)-dione in the total yield over 88 %. The said process uses easy-to-obtain material, has mild reaction condition and is suitable for industrial production.

Description

technical field [0001] The invention belongs to the field of organic chemistry and is (3aS, 6aR)-1,3-dibenzyl-tetrahydro-4H-furo[3,4-d]imidazole-2,4(1H)-diketone (I) synthetic method. Background technique [0002] (3aS,6aR)-1,3-Dibenzyl-tetrahydro-4H-furo[3,4-d]imidazole-2,4(1H)-dione (I) is a synthetic d-biotin (d -Biotin, vitamin H, key intermediate of coenzyme R). [0003] Gerecke et al. (Helv Chim Acta, 1970, 53, 991) reported that cis-1.3-dibenzylimidazolin-2-one-2H-furo[3.4-d]imidazole-2,4,6-trione (cyclo Acid anhydride, II) and cyclohexanol monoesterification to produce racemic cyclic acid monocyclohexanol ester and pseudoephedrine for diastereomeric crystallization (direct enantiomorphous crystallization) to resolve into the required (4S, 5R) -cyclic acid monocyclohexanol ester, and then carry out reduction through lithium borohydride, close the ring to obtain I; this method is the earliest production technology of Swiss Roche to produce d-biotin; German patent ...

AI Technical Summary

Problems solved by technology

These methods all have low single resolution rate, complex operation and high cost resolution. In addition, there are cyclic acid anhydrides and optically active substituting chiral secondary alcohols and tert-butanols (EP, 92194) and cholesterol ( Helv Chim Acta, 1970, 53, 991) formed diastereomer cyclic acid half esters, which were separated by recrystallization to obtain (4S, 5R)-cyclic acid monoesters, and then reduced and ring-closed to prepare I. However, these methods use optically active substituting chiral secondary alcohols, tert-butanols, and cholesterol, which have disadvantages such as difficulty in preparation, high price, or inconvenient recovery.