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

New process for synthesizing N-Boc-4-fluoro-L-proline

A technology of n-boc-4-, synthesis process, applied in the field of medicine and chemical industry, can solve the problems of expensive and difficult to implement on a large scale, and achieve the effects of low production cost, environmental friendliness and high reaction yield

Pending Publication Date: 2022-05-27
南京碳硅人工智能生物医药技术研究院有限公司 +1
View PDF0 Cites 0 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0003] The methods reported in the literature for the preparation of N-Boc-4-fluoro-1-proline are very expensive and difficult to implement on a large scale

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

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0012] Embodiment 1: The novel process of N-Boc-4-fluoro-L-proline synthesis comprises the following steps:

[0013] (1) 500g of p-nitrobenzenesulfonyl chloride was dissolved in two liters of toluene, then 657g of potassium fluoride was dissolved in 1.7L of water, the resulting aqueous solution was poured into the above-mentioned toluene system, and 6g of tetrabutyl fluoride was added subsequently ammonium, react at 60°C for 12 hours, then filter the solids in the system, wash the filtrate three times with 2 liters of water, and spin dry the excess solvent under reduced pressure to obtain p-nitrobenzenesulfonyl fluoride.

[0014] (2) Re-fluorination: 200g of N-Boc-4-hydroxy-L-proline methyl ester was dissolved in 2L of toluene solution, then 268g of DBU was added dropwise within 30 minutes, and the yellow obtained in step (1) was added dropwise. The solid was added to the above system in batches and reacted at 50°C for 12 hours. After cooling to room temperature, wash three t...

Embodiment 2

[0017] Embodiment 2: The novel process of N-Boc-4-fluoro-L-proline synthesis comprises the following steps:

[0018] (1) 5kg p-nitrobenzenesulfonyl chloride is dissolved in two liters of toluene, then the potassium fluoride of 6.57kg is dissolved in 17L water, the resulting aqueous solution is poured into the above-mentioned toluene system, then 60g of tetrabutyl fluoride is added ammonium, react at 60°C for 12 hours, then filter the solids in the system, wash the filtrate three times with 20 liters of water, and spin dry the excess solvent under reduced pressure to obtain p-nitrobenzenesulfonyl fluoride.

[0019] (2) Re-fluorination: 200g of N-Boc-4-hydroxy-L-proline methyl ester was dissolved in 2L of toluene solution, then 268g of DBU was added dropwise within 30 minutes, and the yellow obtained in step (1) was added dropwise. The solid was added to the above system in batches and reacted at 50°C for 12 hours. After cooling to room temperature, wash three times with 1 L of...

Embodiment 3

[0021] Embodiment 3: The novel process of N-Boc-4-fluoro-L-proline synthesis comprises the following steps:

[0022] (1) 500g p-nitrobenzenesulfonyl chloride is dissolved in two liters of toluene, then the potassium fluoride of 657g is dissolved in 1.7L water, the resulting aqueous solution is poured into the above-mentioned toluene system, 6g18-crown-6 is added subsequently, The reaction was carried out at 60°C for 12 hours, then the solids in the system were filtered, the filtrate was washed three times with 2 liters of water, and the excess solvent was spin-dried under reduced pressure to obtain p-nitrobenzenesulfonyl fluoride. 1 H NMR (400MHz, CDCl 3 ): δ8.24-8.8.26(d, 2H), 8.49-8.51(d, 2H).

[0023] (2) Re-fluorination: 200g of N-Boc-4-hydroxy-L-proline methyl ester was dissolved in 2L of toluene solution, then 268g of DBU was added dropwise within 30 minutes, and the yellow obtained in step (1) was added dropwise. The solid was added to the above system in batches and ...

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 novel process for synthesizing N-Boc-4-fluoro-L-proline, which mainly comprises the following steps: taking p-nitrobenzenesulfonyl chloride and potassium fluoride as raw materials to obtain p-nitrobenzenesulfonyl fluoride under the catalytic action of a catalyst, reacting the p-nitrobenzenesulfonyl fluoride with N-Boc-4-hydroxy-L-proline methyl ester under the alkaline condition to obtain the N-Boc-4-fluoro-L-proline. And finally, hydrolyzing under an alkaline condition to obtain the N-Boc-4-fluoro-L-proline. The method is simple, the production cost is greatly reduced, the reaction yield is improved, and meanwhile the technological process is optimized.

Description

technical field [0001] The invention belongs to the field of medicine and chemical industry, in particular to a new process for synthesizing N-Boc-4-fluoro-L-proline. Background technique [0002] 4-Fluoro-proline is an important intermediate in the process of drug synthesis, such as: hepatitis C virus (HCV) inhibitor, HIV-1 protease inhibitor, anti-Alzheimer's disease agent, anti-tumor drug , GABA uptake inhibitors, thrombin inhibitors, peptide deformylase (PDF) inhibitors, TNF-α production inhibitors, pan-light kinase inhibitors, inhibitors of ROS1 and NTRK kinases, GPR119 receptor agonists, VLA-4 inhibitors, and fibroblast activation protein (FAP) inhibitors, etc. [0003] The methods reported in the literature for the preparation of N-Boc-4-fluoro-1-proline are very expensive and difficult to implement on a large scale. SUMMARY OF THE INVENTION [0004] The present invention proposes a new process for synthesizing N-Boc-4-fluoro-L-proline from the viewpoints of optim...

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): C07D207/16
CPCC07D207/16Y02P20/55
Inventor 武松宇张卿袁良超雷德维
Owner 南京碳硅人工智能生物医药技术研究院有限公司
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