Looking for breakthrough ideas for innovation challenges? Try Patsnap Eureka!

Preparation method of (S)-3-hydroxytetrahydrofuran

A technology of hydroxytetrahydrofuran and sodium borohydride, applied in the direction of organic chemistry, can solve the problems of increased product cost, impurities, high reaction temperature, etc., and achieve the effects of increased product yield, omitted rectification steps, and simple post-treatment

Active Publication Date: 2018-04-20
SHANDONG BOYUAN PHARM CO LTD
View PDF4 Cites 7 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

But this method takes a long time to react, the required equipment is complex, and it is difficult to modify the equipment in production, so it is not suitable for industrial production.
[0009] In the above-mentioned process, when butanetriol is dehydrated and ring-closed at high temperature under the action of p-toluenesulfonic acid, the reaction temperature is high (up to 200°C), and the target product is prone to configuration inversion under acidic conditions, resulting in isomers. Dehydration and oxidation reactions occur to produce impurities (the reaction equation is shown below)
The method of rectification with alkali is usually used to purify the product, but the yield is not high, which increases the cost of the product

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
  • Preparation method of (S)-3-hydroxytetrahydrofuran
  • Preparation method of (S)-3-hydroxytetrahydrofuran
  • Preparation method of (S)-3-hydroxytetrahydrofuran

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0039] 1) Add 280mL methanol, 168g (1.25mol) L-malic acid to a 1000ml reaction flask, reduce it to 0°C, add 202mL thionyl chloride dropwise to the temperature below 0°C, and then raise it to room temperature after dripping, and react with stirring for 24 hours; After the reaction is completed, the methanol is evaporated at 40-45°C.

[0040] 2) Add 215 g (1.25 mol) of benzyl bromide and 2 g of silver oxide to the obtained oil, stir and react at room temperature for 6 hours, and filter with suction.

[0041] 3) Add 600 mL of tetrahydrofuran and 44 g of sodium borohydride to the reaction flask, lower the temperature to 0°C, and control the temperature at about 0°C to drop the mother liquor obtained in the step. After dripping, the reaction was kept at 0°C for 18 hours. After the reaction, tetrahydrofuran was distilled off, the pH was adjusted to 2 with concentrated hydrochloric acid, 300 mL of ethyl acetate was added for extraction, and the mixture was concentrated under reduced pres...

Embodiment 2

[0045] 1) Add 260 mL of methanol and 168 g (1.25 mol) of L-malic acid to a 1000 ml reaction flask, reduce to 0°C, add 200 mL of thionyl chloride dropwise to control the temperature below 0°C, and then raise to room temperature after dropwise, and react with stirring for 27 hours. After the reaction is completed, the methanol is evaporated at 40-45°C.

[0046] 2) Add 215 g (1.25 mol) of benzyl bromide and 2 g of silver oxide (recovered) to the obtained oil, stir and react at room temperature for 5 hours, and filter with suction.

[0047] 3) Add 500 mL of tetrahydrofuran and 44 g of sodium borohydride to the reaction flask, lower the temperature to 0°C, and control the temperature at about 0°C to drop the mother liquor obtained in the step. After dripping, keep the reaction at 0°C for 20 hours. After the reaction, the tetrahydrofuran was distilled off, the pH was adjusted to 2 with concentrated hydrochloric acid, 280 mL of ethyl acetate was added for extraction, and the mixture was ...

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 a preparation method of (S)-3-hydroxytetrahydrofuran. The problems that butantriol is difficult to separate in the production process, the yield is not high and the impurity content and the isomer content of the products are high are mainly solved. The preparation method of (S)-3-hydroxytetrahydrofuran comprises the following steps: under the existence of sulfoxide chloride, malic acid reacts with methanol to generate a compound II; under the existence of silver oxide, performing reaction on the compound II and benzyl bromide to generate a compound III; reducing the compound III by sodium borohydride to generate a compound IV; performing dehydration and ring closing on the compound IV by p-toluenesulfonic acid to generate a compound V; and taking palladium carbon asa catalyst and performing hydrogen reduction treatment on the compound V to obtain the product. The method is simple in aftertreatment and environment-friendly; the yield of the products is increasedby 80 percent or more, the purity is more than 99.5 percent and the chiral purity is more than 99.2 percent; and the method is suitable for industrialized production. (The formulas are as shown in the description).

Description

Technical field [0001] The invention relates to a preparation method of (S)-3-hydroxytetrahydrofuran, which belongs to the technical field of organic synthesis. Background technique [0002] (S)-3-Hydroxytetrahydrofuran is an important intermediate for the diabetes drug enpagliflozin, the anti-tumor drug Alfatinib and the synthesis of anti-AIDS drugs. It can also be used to synthesize pesticides and can significantly improve the weeding of diphenyl ether herbicides. Activity and selectivity have high economic value. [0003] At present, the synthesis process of (S)-3-hydroxytetrahydrofuran is mainly: L-malic acid is used as the starting material, and the methyl esterification reaction with thionyl chloride / methanol produces (S)-malic acid dimethyl ester, and then Reduction with sodium borohydride to generate (S)-1,2,4-butanetriol, and finally toluenesulfonic acid dehydration and ring closure to generate (S)-3-hydroxytetrahydrofuran. The chemical reaction equation is as follows: ...

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
Patent Type & Authority Applications(China)
IPC IPC(8): C07D307/20
CPCC07D307/20
Inventor 赵希伟昝金行刘茂盛
Owner SHANDONG BOYUAN PHARM CO LTD
Who we serve
  • R&D Engineer
  • R&D Manager
  • IP Professional
Why Patsnap Eureka
  • Industry Leading Data Capabilities
  • Powerful AI technology
  • Patent DNA Extraction
Social media
Patsnap Eureka Blog
Learn More
PatSnap group products

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

© 2024 PatSnap. All rights reserved.Legal|Privacy policy|Modern Slavery Act Transparency Statement|Sitemap|About US| Contact US: help@patsnap.com