Method for preparing (3S,6aR)-1,3-dibenzyl-tetrahydro-1H-thieno [3,4-d] imidazole-2(3H)-ketone-4-normal pentanoic acid

A technology of dibenzyl and n-valeric acid, applied in the direction of organic chemistry, can solve the problems of difficult preparation, and achieve the effect of simple operation, convenient preparation and high yield

Inactive Publication Date: 2003-10-01
FUDAN UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

The preparation of ethyl 5-zinc iodovalerate in this method is difficult and expensive triphenylphosphopalladium chloride is used as catalyst

Method used

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Examples

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Effect test

example 1

[0017] Example 1 Magnesium chips (12g, 0.50mol) and methyl tert-butyl ether (120mL) were placed in a dry reaction flask, and after heating and stirring to reflux, 1,4-dibromobutane (105.8g, 0.49mol) was added dropwise to dissolve Add a solution of methyl tert-butyl ether (380mL), drop it within 1.5~2h, continue to stir and reflux until there is almost no magnesium chips (about 2.5~3h), cool to room temperature, then cool to -15°C, drop Add (3aS, 6aR)-1,3-dibenzyl-tetrahydro-4H-thieno[3,4-d]imidazole-2,4(1H)-dione (55.3g, 0.163mol) in methanol The solution of tert-butyl ether (700mL) was dropped within 2~3h, and carbon dioxide was introduced for 3h under heat preservation and stirring, and carbon dioxide was introduced for another 3h at 30~35°C, and the stirring was continued for 1.5h. After the reaction was completed, 5% hydrochloric acid (300 mL) was added to the reactant, stirred at room temperature for 15 min, the organic layer was separated, the aqueous layer was extracted...

example 2

[0018]Example 2 Magnesium chips (12g, 0.50mol), methyl tert-butyl ether (100mL) and anhydrous toluene (250mL) were placed in a dry reaction flask, and after heating and stirring to reflux, 1,4-dichlorobutane ( 113.8g, 0.90mol) in a solution of methyl tert-butyl ether (250mL), drop it within 2h, continue to stir and reflux until almost no magnesium chips (about 3.5h), cool to room temperature, then cool to - -30°C, (3aS, 6aR)-1,3-dibenzyl-tetrahydro-4H-thieno[3,4-d]imidazole-2,4(1H)-dione (55.3g, 0.163 mol) dissolved in toluene (250mL), after dropping within 2h, carbon dioxide was introduced at -30°C for 4h under stirring, and carbon dioxide was introduced at 45°C for another 4h, and stirring was continued for 2h. After the reaction was completed, 5% hydrochloric acid (280 mL) was added to the reactant, stirred at room temperature for 10 min, the organic layer was separated, the aqueous layer was extracted with toluene (80 mL×4), the organic layers were combined, and methyl ter...

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Abstract

A process for preparing (3aS, 6aR)-1,3-bibenzyl- tetrahydro-1H-thieno [3,4-d] imidazole-2(3H)-one-4- n-pentanoic acid includes such steps as Grignand reaction of (3aS, 6aR)-1,3-bibenzyl-tetrahydro-4H- thieno [3,4-d] imidazole-2,4(1H)-dione on 1,4-dimagnesium halobutane in organic solution, introducing Co2, carboxylation reaction to obtain (3aS, 6aR)-1,3-bibenzyl-4-n-pentanoic acid, and high steroselective catalytic hydrogenating in organic solvent to obtain (3aS, 4S, 6aR)-1,3-bibenzyl- tetrahydro-1H-thieno[3,4-d] imidazole-2(3H)-one-4-n- pentanoic acid. Its output is higher than 90% and its ee is higher than 97.5%.

Description

technical field [0001] The invention belongs to the field of organic chemistry and is (3aS, 6aR)-1,3-dibenzyl-tetrahydro-1H-thieno[3,4-d]imidazol-2(3H)-one-4-n-pentanoic acid (Dibenzyl biotin, I) preparation method. Background technique [0002] (3aS,6aR)-1,3-Dibenzyl-tetrahydro-1H-thieno[3,4-d]imidazol-2(3H)-one-4-n-pentanoic acid (dibenzyl biotin, I) It is a key intermediate in the synthesis of d-biotin (d-Biotin, vitamin H, coenzyme R). European Patent 015425 describes the combination of (3aS,6aR)-1,3-dibenzyl-tetrahydro-4H-thieno[3,4-d]imidazole-2,4(1H)-dione (II) with bromine (Chloro) 4-(2,4,10-trioxoadamantyl) butyl magnesium is introduced into a five-carbon side chain containing a potential carboxyl functional group in one step through Grignard reaction, followed by dehydration, hydrolysis and reduction to prepare I. The most prominent weakness of this method is that the cis-1,3,5-cyclohexanetriol of bromo(chloro) 4-(2,4,10-trioxoadamantyl) butyl magnesium Grigna...

Claims

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Application Information

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IPC IPC(8): C07D495/04
Inventor 陈芬儿
Owner FUDAN UNIV
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