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

4-acetoxypiperidine hydrochlorate preparation method

A technology of acetoxypiperidine and tert-butoxycarbonylpiperidine, which is applied in the field of synthesis of 4-acetoxypiperidine hydrochloride, can solve the problems of heterogeneity and low reaction yield, and achieve high yield Improved effect

Inactive Publication Date: 2006-04-26
AFFILIATED HUSN HOSPITAL OF FUDAN UNIV
View PDF0 Cites 8 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0006] The purpose of the present invention is to solve the preparation technology of PET imaging agent, specifically to provide a kind of preparation method of 4-acetoxypiperidine hydrochloride, to overcome the heterogeneous reaction system in the prior art, the reaction yield is low etc. shortcoming

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
  • 4-acetoxypiperidine hydrochlorate preparation method
  • 4-acetoxypiperidine hydrochlorate preparation method
  • 4-acetoxypiperidine hydrochlorate preparation method

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0035] Preparation of 4-hydroxy-N-tert-butoxycarbonylpiperidine (2) (Ming-Rong Zhang literature method):

[0036] 10.0g (72.73mmol) of 4-hydroxypiperidine hydrochloride was dissolved in 20ml of distilled water, 50ml of 0.5N NaOH solution was added and 18g (82.57mmol) of di-tert-butyl dicarbonate was added in batches, and vigorously stirred at 25°C for 1 hour, The reaction was extracted with chloroform, the chloroform layer was washed with water, 27% ammonia water, and saturated sodium chloride, the organic layer was dried over anhydrous sodium sulfate, and the solvent was evaporated under reduced pressure to obtain a light yellow oil, which was confirmed to be 4-hydroxypiperidine by structure , the reason for the analysis was that the reaction system was not alkaline enough, so the product required for the experiment did not react.

Embodiment 2

[0038] Preparation of 4-hydroxy-N-tert-butoxycarbonylpiperidine (2):

[0039] 10.0g (72.73mmol) of 4-hydroxypiperidine hydrochloride was dissolved in 80ml of 1N NaOH, under ice cooling, 18g (82.57mmol) of di-tert-butyl dicarbonate was added in batches, and at the same time, 1N NaOH was used to adjust the pH to maintain 8-9 (approximately 100ml 1N NaOH), remove the ice bath after adding, stir overnight at room temperature, extract with chloroform (4×100ml), combine the chloroform layers, wash with water, 7% ammonia water, and saturated sodium chloride three times each, and anhydrous sulfuric acid for the organic layer After drying over sodium, the solvent was distilled off under reduced pressure to obtain a pale yellow oil, which solidified after standing overnight to 11.0 g, with a yield of 75.0%. The product can be directly carried out to the next step without purification.

Embodiment 3

[0041] Preparation of 4-hydroxy-N-tert-butoxycarbonylpiperidine (2):

[0042] 10.0g (72.73mmol) of 4-hydroxypiperidine hydrochloride was dissolved in 80ml of 1N NaOH and 100ml of 1,4-dioxane, under ice cooling, 18g (82.57mmol) of di-tert-butyl dicarbonate was added in batches , while using 1N NaOH to adjust the pH to maintain 7-8 (approximately 100ml 1NNaOH), remove the ice bath after adding, stir at room temperature overnight, then add 100ml of water, evaporate 1,4-dioxane under reduced pressure, and extract with chloroform ( 4 × 100ml), the chloroform layers were combined, washed three times with water, 7% ammonia water, and saturated sodium chloride, the organic layer was dried over anhydrous sodium sulfate, and the solvent was evaporated under reduced pressure to obtain a light yellow oil, which solidified after standing overnight. 14.0g, The yield was 94.0%, and the product could be directly carried out to the next reaction without purification.

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 present invention belongs to the field of chemical synthesis, relates to PET image developer preparing technology, and is especially the synthesis process of 4-acetoxyl piperidine (P4A) hydrochloride. The present invention adopts 4-hydroxyl piperidine hydrochloride as main material, pyrocarbonic acid di-tert-butyl ester in homogeneous alkaline reaction system for amino radical protection and acetic anhydride to acetylate hydroxyl radical before eliminating protecting radical, and introduces dry hydrogen chloride gas into anhydrous ethyl ether to obtain 4-acetoxyl piperidine (P4A) hydrochloride as the destination product. The process has high destination product yield of 71 %, mild reaction condition and simple operation.

Description

technical field [0001] [ 11 C] methylpiperidine ([ 11 C]-MP4A) labeling precursor provides a basis for the further preparation of PET molecular imaging drugs of brain acetylcholinesterase. Background technique [0002] Positron emission tomography (PET) can be used for brain imaging with high sensitivity and good resolution. In the imaging study of acetylcholine (Ach) in the brain, it was recently discovered abroad that 11 C-labeled ACh congeners (such as [ 11 C]-MP4P, [ 11 C]-MP4A, [ 18 After F]-FETP4A) enters the human brain, the activity of acetylcholinesterase (Acetylcholinesterase, AChE) can be reflected by PET imaging. Studies have confirmed that the progressive loss of cortical acetylcholinesterase activity inassociation with cognitive decline in Alzheimer's disease: a progressive loss of cortical acetylcholinesterase activity inassociation with cognitive decline in Alzheimer's disease. positron emissiontomography study. Annals neurol 2000, 48: 194-200.). ACh ...

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): C07D211/62
Inventor 蒋雨平胡名扬王坚管一晖
Owner AFFILIATED HUSN HOSPITAL OF FUDAN UNIV
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