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

Method for preparing intermediates for synthesizing 25-hydroxyvitamin D2 and 1 alpha, 25-dihydroxyvitamin D2

A technology of dihydroxyvitamin and hydroxyvitamin, which is applied in the field of preparation of two organic compounds, can solve the problems of low yield, limitation, difficulty in synthesis and purification, etc.

Inactive Publication Date: 2012-08-22
SHANGHAI HAOYUAN CHEMEXPRESS
View PDF6 Cites 6 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Compound 8 not only has a low yield when it is used for drug synthesis, but also the synthesis and purification of compound 3 itself is difficult, and its synthesis process also causes some limitations for the protective group R functional group

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
  • Method for preparing intermediates for synthesizing 25-hydroxyvitamin D2 and 1 alpha, 25-dihydroxyvitamin D2
  • Method for preparing intermediates for synthesizing 25-hydroxyvitamin D2 and 1 alpha, 25-dihydroxyvitamin D2
  • Method for preparing intermediates for synthesizing 25-hydroxyvitamin D2 and 1 alpha, 25-dihydroxyvitamin D2

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0026] Example 1: Preparation methods of compounds 2a-1, 2b-1, 3a-1 and 3b-1. where R is phenyl, R 2 is tert-butyldimethylsilyl, R 3 For trimethylsilyl; R in 2a-1 and 3a-1 1 is a hydrogen atom, R in 2b-1 and 3b-1 1 Be methoxymethoxy, its reaction formula is as follows respectively (formula 5):

[0027]

[0028]

[0029] Formula 5

[0030] Dissolve 600 mg of compound 9-1 in 10 mL of anhydrous tetrahydrofuran, cool to minus 78 degrees Celsius under nitrogen protection, and then slowly drop 1.0 mL of 1.6 mol / L butyllithium in tetrahydrofuran solution into it. The reaction was stirred for 30 minutes, and then 500 mg of 5a-1 tetrahydrofuran solution was slowly dropped into it below -40 degrees Celsius, and the reaction was continued for 2 hours with stirring. Naturally raised to room temperature, quenched with saturated ammonium chloride, extracted with ethyl acetate, the organic phase was dried over anhydrous sodium sulfate, concentrated, and the residue was subjected t...

Embodiment 2

[0032] Example 2: Preparation methods of compounds 2a-2, 2b-2, 3a-2 and 3b-2. Where R is p-tolyl, R 2 is methoxymethyl, R 3 For 2-tetrahydropyranyl; R in 2a-2 and 3a-2 1 is a hydrogen atom, R in 2b-2 and 3b-2 1 Be triethylsilyloxy group, its reaction formula is as follows respectively (formula 6):

[0033]

[0034] Formula 6

[0035]Dissolve 800 mg of compound 9-2 in 10 mL of anhydrous tetrahydrofuran, cool to minus 78 degrees Celsius under nitrogen protection, and then slowly drop 2.5 mL of 1.0 mol / L tetrahydrofuran solution of tert-butyllithium into it. Continue to stir and react for 30 minutes, and then slowly drop 640 mg of 5a-2 tetrahydrofuran solution into it below -70 degrees Celsius, and continue to stir and react for 2 hours. Naturally raised to room temperature, quenched with saturated ammonium chloride, extracted with ethyl acetate, the organic phase was dried over anhydrous sodium sulfate, concentrated, and the residue was subjected to silica gel column chr...

Embodiment 3

[0037] Example 3: Preparation methods of compounds 2a-3, 2b-3, 3a-3 and 3b-3. where R is methoxy, R 2 is 2-tetrahydrofuranyl, R 3 For methoxymethyl; R in 2a-3 and 3a-3 1 is a hydrogen atom, R in 2b-3 and 3b-3 1 Be benzoyloxy group, its reaction formula is as follows respectively (formula 7):

[0038]

[0039] Formula 7

[0040] Take 100 mg of sodium hydride and add it to 10 mL of anhydrous n-hexane, cool it to zero degrees Celsius under the protection of nitrogen, and then slowly add 800 mg of compound 9-3 in n-hexane solution dropwise therein. Then, 700mg of 5a-3 n-hexane solution was slowly dropped into it at 0°C, and the stirring reaction was continued for 5h. Naturally raised to room temperature, quenched with water, extracted with ethyl acetate, the organic phase was dried over anhydrous sodium sulfate, concentrated, and the residue was subjected to silica gel column chromatography to obtain 0.60 g of 2a-3 respectively.

[0041] In the same way, 700mg of 5b-3 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 method for preparing intermediates for 25-hydroxyvitamin D2 and 1 alpha, 25-dihydroxyvitamin D2. The structures of the intermediates are compounds 2 and 3 shown as the following formula 1. The preparation method is shown as the following formulas, and comprises the following steps of: treating a phosphorus oxide 9 by using strong base, and performing a Wittig-Hormer reaction with aldehyde 5 or 6. Formula 1.

Description

technical field [0001] The present invention relates to a process for the preparation of two organic compounds, specifically 25-hydroxyvitamin D 2 and 1α, 25-dihydroxyvitamin D 2 method of preparation. Background technique [0002] [0003] Formula 1 [0004] 25-Hydroxyvitamin D as shown in Formula 1 2 and 1α, 25-dihydroxyvitamin D 2 , both are regulators of calcium and phosphorus homeostasis in animals and humans 1，2 . Recent studies have also identified their activity in cell recognition 3，4，5 . Therefore, various types of 25-hydroxyvitamin D analogs have aroused widespread interest of researchers, such as derivatives of vitamin D side chains, analogs of different hydroxyl models, analogs of different stereo configurations, etc., are widely used Applied to various types of activity tests, many known compounds of this type have demonstrated good activity in vitro and in vivo, showing good application effects and potential applications in the treatment of various ...

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): C07F7/18C07D309/12C07D307/20C07C43/188C07C41/30C07C69/78C07C67/293
Inventor 郑保富薛吉军高强张宪恕刘荣刘海旺
Owner SHANGHAI HAOYUAN CHEMEXPRESS
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