Check patentability & draft patents in minutes with Patsnap Eureka AI!

An improved method for debenzylation and synthesis of d-biotin

A technology of bisbenzyl biotin and biotin, applied in the direction of organic chemistry, etc., can solve the problems of increasing sodium dosage, difficulty and seriousness of workshop production control, and achieves the effect of high yield

Active Publication Date: 2017-08-15
ZHEJIANG MEDICINE CO LTD XINCHANG PHAMACEUTICAL FACTORY
View PDF2 Cites 2 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, there are still some problems in this method, which are as follows: (1) 10-20 hours, 120-130°C debenzylation conditions are required, heating for a long time, and the production equipment is corroded quite seriously
(2) The continuous production of benzyl bromide, a by-product of debenzylation, is a strong lachrymator, and the glass-lined equipment used in production is prone to produce more leakage points, making it difficult to control the production in the workshop
But this method also has a fatal flaw, that is: no matter how the conditions are changed, or the amount of sodium is greatly increased, it cannot be debenzylated completely, and about 30% of monobenzyl biotin remains, which has been impossible for many years. Reasons for Industrialization

Method used

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
View more

Image

Smart Image Click on the blue labels to locate them in the text.
Viewing Examples
Smart Image
  • An improved method for debenzylation and synthesis of d-biotin
  • An improved method for debenzylation and synthesis of d-biotin
  • An improved method for debenzylation and synthesis of d-biotin

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0032] Embodiment 1 The normal complete debenzylation process of the present invention is divided into three steps:

[0033] (1) Preparation of monobenzyl biotin by debenzylation of metal sodium in liquid ammonia

[0034] Take 23g of bisbenzylbiotin (HPLC content 92%, 0.05mol), dissolve it in 50mL of toluene, put it in a 500mL reaction bottle, protect it with nitrogen gas, and cool it with -40°C cryogenic ethanol externally, add liquid ammonia to the reaction bottle 300g, add sodium metal 2.8g (0.12mol) in batches under stirring, after adding sodium metal for the last time, after the color of the reaction solution changes from blue to milky white, after the reaction is complete, add solid ammonium chloride 6.4g, stir for more than one hour, Remove the ice bath, heat in a water bath to volatilize and evaporate the ammonia gas, add 100 mL of water to the residue, adjust the pH value to 2-4 with hydrochloric acid, and precipitate a solid. 16.5 g was obtained by drying, and the c...

Embodiment 2

[0040] Example 2 In the first step, the amount of sodium metal is more

[0041] (1) Preparation of monobenzyl biotin and biotin mixture by debenzylation of metal sodium in liquid ammonia

[0042] Take 23g of bisbenzylbiotin (HPLC content 92%, 0.05mol), dissolve it in 50mL of toluene, put it in a 500mL reaction bottle, protect it with nitrogen gas, and cool it with -40°C cryogenic ethanol externally, add liquid ammonia to the reaction bottle 300g, add sodium metal 4.2 (0.18mol) g in batches under stirring, after adding sodium metal for the last time, after the color of the reaction solution changes from blue to milky white, after the reaction is complete, add solid ammonium chloride 9.6g, stir for more than one hour, Remove the ice bath, heat in a water bath to volatilize and evaporate the ammonia gas, add 100 mL of water to the residue, adjust the pH value to 2-4 with hydrochloric acid, and precipitate a solid. Dry to obtain 15.8 g, the content of biotin detected by HPLC is 1...

Embodiment 3

[0048] Embodiment 3 In the first step, the sodium metal consumption is less

[0049] (1) Preparation of monobenzyl biotin by debenzylation of metal sodium in liquid ammonia

[0050] Take 23g of bisbenzylbiotin (HPLC content 92%, 0.05mol), dissolve it in 50mL of toluene, put it in a 500mL reaction bottle, protect it with nitrogen gas, and cool it with -40°C cryogenic ethanol externally, add liquid ammonia to the reaction bottle 300g, add sodium metal 2.3g (0.1mol) in batches under stirring, after adding sodium metal for the last time, after the color of the reaction solution changes from blue to milky white, the reaction is complete, add solid ammonium chloride 9.6g, stir for more than one hour, Remove the ice bath, heat in a water bath to volatilize and evaporate the ammonia gas, add 100 mL of water to the residue, adjust the pH value to 2-4 with hydrochloric acid, and precipitate a solid. 16.8 g was obtained by drying, the content of dibenzyl biotin was 5.2% and the content ...

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
Login to View More

PUM

No PUM Login to View More

Abstract

The invention discloses an improved d-biotin debenzylation synthesizing method. As for existing methods in which biotin is prepared in liquid ammonia in a debenzylation mode through metallic sodium, debenzylation can not be complete. According to the technical scheme, the method includes the steps that firstly, debenzylation is carried out on double-benzyl biotin in liquid ammonia through metallic sodium to form single-benzyl biotin; secondly, the single-benzyl biotin is reacted with silicane protective agents, and amidogen and carboxyl of the single-benzyl biotin are protected to obtain group protectors of the single-benzyl biotin; thirdly, debenzylation is carried out on the group protectors of the single-benzyl biotin in the liquid ammonia through the metallic sodium again, acid neutralization and deprotection are carried out, and complete-debenzylation crude d-biotin is obtained; finally, the crude biotin is refined to obtain the fine d-biotin. According to the method, debenzylation is almost complete, the yield of the d-biotin is high, and the method is quite suitable for industrial production.

Description

technical field [0001] The invention relates to the field of organic chemical synthesis, in particular to an improved method for synthesizing d-biotin through debenzylation. Background technique [0002] Biotin, also known as vitamin H or coenzyme R, is a water-soluble B vitamin. The total synthesis of biotin was completed for the first time in 1944, and the biotin currently available on the market is prepared by chemical total synthesis. The chemical total synthesis of biotin has many reaction steps and difficult process. The stereoselective total synthesis of d-biotin is a challenging research topic in the field of organic chemistry. [0003] So far, a number of total synthetic routes of d-biotin have been developed, but the Goldberg-Sternbach route is still recognized as having the most industrial value. In 1949, US2489238 disclosed this famous total synthetic route. Using fumaric acid as the starting material, a chiral lactone was obtained through a multi-step reaction...

Claims

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
Login to View More

Application Information

Patent Timeline
no application Login to View More
IPC IPC(8): C07D495/04
Inventor 皮士卿王业节郭东初张伟峰潘夏峰
Owner ZHEJIANG MEDICINE CO LTD XINCHANG PHAMACEUTICAL FACTORY
Features
  • R&D
  • Intellectual Property
  • Life Sciences
  • Materials
  • Tech Scout
Why Patsnap Eureka
  • Unparalleled Data Quality
  • Higher Quality Content
  • 60% Fewer Hallucinations
Social media
Patsnap Eureka Blog
Learn More

Browse by: Latest US Patents, China's latest patents, Technical Efficacy Thesaurus, Application Domain, Technology Topic, Popular Technical Reports.

© 2025 PatSnap. All rights reserved.Legal|Privacy policy|Modern Slavery Act Transparency Statement|Sitemap|About US| Contact US: help@patsnap.com