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

The preparation method of bazedoxifene acetate intermediate

A technology for bazedoxifene acetate and intermediates, which is applied in the field of preparation of bazedoxifene acetate intermediates, and can solve problems such as poor product purity, high toxicity, and poor atom economy

Active Publication Date: 2016-10-05
SHANGHAI INST OF PHARMA IND CO LTD +2
View PDF8 Cites 2 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0015] The technical problem to be solved by the present invention is to overcome the preparation method route of existing 4-[2-(cyclohexylimino-1-)ethoxyl]benzyl chloride hydrochloride is relatively long, and the price of raw materials is relatively expensive. The method has defects such as harsh reaction conditions, high toxicity, serious environmental pollution, poor atom economy, low reaction yield, poor product purity, etc., and a preparation method for bazedoxifene acetate intermediate is provided

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
  • The preparation method of bazedoxifene acetate intermediate
  • The preparation method of bazedoxifene acetate intermediate
  • The preparation method of bazedoxifene acetate intermediate

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 14-

[0056] Preparation of Example 14-[2-(cyclohexylimino-1-yl)ethoxy]benzyl alcohol 3

[0057] Under the protection of nitrogen, add sodium tert-butoxide (24.2g, 253mmol) into DMF (150mL), stir for 30min, add a solution of p-hydroxybenzaldehyde (16.6g, 136mmol) in DMF (80mL) dropwise at 0°C, dropwise, keep warm (0°C) Stir for 30min. 2-(Cyclohexylimino)ethyl chloride hydrochloride (25g, 124mmol) was added at 0°C. After the addition was complete, the temperature was raised to 25°C for 4h. TLC tracking showed that the reaction of 2-(cyclohexylimino)ethyl chloride hydrochloride was complete, methanol (110mL) was added to the reaction solution, the temperature dropped to 0°C, and sodium borohydride (2.7g, 69.6mmol) was added in batches , After addition, react at 25°C for 2 hours. The reaction solution was poured into ice water (200 mL), extracted with ethyl acetate (100 mL×3), washed with saturated sodium chloride solution, dried over anhydrous sodium sulfate, and concentrated under ...

Embodiment 24-

[0058] Preparation of Example 24-[2-(cyclohexylimino-1-yl)ethoxy]benzyl alcohol 3

[0059] Under the protection of nitrogen, sodium hydride (10.1g, 253mmol) was added to DMF (80mL), stirred for 10min, and a solution of p-hydroxybenzaldehyde (16.6g, 136mmol) in DMF (80mL) was added dropwise at 0°C. ℃) and stirred for 30 minutes. 2-(Cyclohexylimino)ethyl chloride hydrochloride (25g, 124mmol) was added at 0°C. After the addition was complete, the temperature was raised to 25°C for 2h. TLC tracking showed that the reaction of 2-(cyclohexylimino)ethyl chloride hydrochloride was complete, ethanol (100mL) was added to the reaction solution, the temperature dropped to 0°C, and sodium borohydride (2.7g, 69.6mmol) was added in batches After the addition was completed, the reaction was carried out at room temperature at 25°C for 2 hours. The reaction solution was poured into ice water (200 mL), extracted with ethyl acetate (100 mL×3), washed with saturated sodium chloride solution, dri...

Embodiment 34-

[0060] Preparation of Example 34-[2-(cyclohexylimino-1-)ethoxy]benzyl chloride hydrochloride 1

[0061] Under the protection of nitrogen, add anhydrous methanol (0.7mL, 17mmol) into the three-necked flask, lower the temperature to 0°C, slowly add acetyl chloride (1.2mL, 17mmol) dropwise, keep warm (0°C) and stir for 30min, and 4-[2 -(Cyclohexylimin-1-yl)ethoxy]benzyl alcohol (4.3g, 17mmol) in THF (10mL) was slowly added dropwise to the above solution, and a white solid was formed. When the solid no longer increases, add thionyl chloride (1.8mL, 25mmol) dropwise at the same temperature. After the drop is completed, the temperature is raised to 50°C, and the solid gradually dissolves. TLC tracking shows that 4-[2-(cyclohexylimine-1- Base) ethoxyl] benzyl alcohol hydrochloride is completely reacted, concentrated under reduced pressure to half of the solution volume, refrigerated overnight at 0°C, filtered with suction, and dried to obtain 4.5 g of light yellow solid 4-[2-(cyclohe...

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 bazedoxifene acetate intermediate. The present invention provides a preparation method of bazedoxifene acetate intermediate compound 3, and the preparation method comprises the following steps: step 1, in a polar aprotic solvent in the presence of an alkali, intermediate compound 4 is obtained by condensation reaction of p-hydroxy benzaldehyde 6 and compound 5; and step 2, the reaction solution obtained in step 1, without after treatment, is directly mixed with a protic solvent, then is reduced by a reductant to obtain the bazedoxifene acetate intermediate compound 3. The preparation method has the advantages of short course, mild reaction conditions, safe operation, simple post treatment process, high conversion rate, high product yield, good purity, environmental friendliness and suitability for industrialized production.

Description

technical field [0001] The invention relates to a preparation method of a bazedoxifene acetate intermediate. Background technique [0002] Bazedoxifene developed by Wyeth Company is a new generation of SERM, which can competitively inhibit the binding of 17β-estradiol to ERα and ERβ, and has no agonist activity on human breast cancer cell lines when used alone. Preclinical tests show that it is superior to raloxifene (second generation SERM) and lasofoxifene (third generation SERM) in improving uterine properties among similar products, and the vasomotor instability model Tests show that its central nervous system side effects are very small, and it is a relatively effective agonist in activating the hepatic lipase promoter, while raloxifene is ineffective. When combined with raloxifene, it can Inhibiting the stimulating effect of raloxifene on the uterus of rodents, it can be seen that the effects of the two on the uterus are different. Preclinical test data show that it ...

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 Patents(China)
IPC IPC(8): C07D295/088
CPCC07D295/088
Inventor 陈姗袁哲东刘相奎孔锐张喜全王善春
Owner SHANGHAI INST OF PHARMA IND 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