Preparation method for trans-4-alkoxycyclohexylamine

A technology of alkoxycyclohexylamine and hydroxycyclohexylamine, which is applied in the field of pharmaceutical intermediates, can solve the problems of high product loss, low product yield, and difficult operation, and achieve high total yield, environmental friendliness, and easy measurement produced effect

Active Publication Date: 2018-01-12
SHANGHAI BALMXY PHARMA CO LTD
View PDF2 Cites 0 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0011] However, in this route, the tert-butoxycarbonyl group causes more product loss during the protection and deprotection process, and at the same time, due to its own melting point problem, it is not conducive to the operation in industrial production, and in the process of methyl

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 for trans-4-alkoxycyclohexylamine
  • Preparation method for trans-4-alkoxycyclohexylamine
  • Preparation method for trans-4-alkoxycyclohexylamine

Examples

Experimental program
Comparison scheme
Effect test

Example Embodiment

[0058] Example 1

[0059] In this embodiment, trans 4-methoxycyclohexylamine is prepared by the following preparation method, which includes the following steps:

[0060] (1) Preparation of trityl-protected trans-4-hydroxycyclohexylamine:

[0061]

[0062] Trans-4-hydroxycyclohexylamine (115g, 1mol) was dissolved in dichloromethane (2L), triethylamine (121g, 1.2mol) was added with stirring, and the reaction system dropped to zero. Then trityl chloride (284g, 1.02mol) was added portion by portion, and the reaction was slowly warmed to room temperature and stirred for 5 hours. The reaction solution was washed with 10% citric acid, washed with saturated brine, and dried with anhydrous sodium sulfate to obtain an almost white color. The powder was crystallized with ethyl acetate and petroleum ether to obtain 332 g of pure product with a yield of 93%.

[0063] (2) Preparation of trityl-protected trans 4-methoxycyclohexylamine:

[0064]

[0065] The compound (250g, 0.7mol) obtained in step ...

Example Embodiment

[0070] Example 2

[0071] In this embodiment, trans 4-isopropoxycyclohexylamine is prepared by the following steps, and the method includes the following steps:

[0072] (1) Preparation of trityl-protected trans-4-hydroxycyclohexylamine:

[0073]

[0074] Trans-4-hydroxycyclohexylamine (115g, 1mol) was dissolved in dichloromethane (2L), triethylamine (151.25g, 1.5mol) was added with stirring, and the reaction system dropped to zero. Then add trityl chloride (278g, 1mol) portion by portion, the reaction is slowly warmed to room temperature and stirred for 10 hours, the reaction solution is washed with 10% citric acid, washed with saturated brine, and dried with anhydrous sodium sulfate to obtain a white powder , Crystallized with ethyl acetate petroleum ether to obtain 327 g of pure product with a yield of 91.6%.

[0075] (2) Preparation of trityl-protected trans 4-isopropoxycyclohexylamine:

[0076]

[0077] The compound (250g, 0.7mol) obtained in step (1) was dissolved in 2L tetrahy...

Example Embodiment

[0082] Example 3

[0083] In this embodiment, trans 4-butoxycyclohexylamine is prepared by the following steps, and the method includes the following steps:

[0084] (1) Preparation of trityl-protected trans-4-hydroxycyclohexylamine:

[0085]

[0086] Dissolve trans-4-hydroxycyclohexylamine (115g, 1mol) in dichloromethane (2L), add triethylamine (101g, 1mol) under stirring, and reduce the reaction system to zero. Then add trityl bromide (505g, 1.5mol) portion by portion, the reaction is slowly warmed to room temperature and stirred for 1 hour, the reaction solution is washed with 10% citric acid, washed with saturated brine, and dried with anhydrous sodium sulfate to obtain an off-white The powder was crystallized with ethyl acetate and petroleum ether to obtain 306 g of pure product with a yield of 85.7%.

[0087] (2) Preparation of trityl-protected trans-4-butoxycyclohexylamine:

[0088]

[0089] The compound (250g, 0.7mol) obtained in step (1) was dissolved in 2L tetrahydrofuran, ...

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 provides a preparation method for trans-4-alkoxycyclohexylamine. The method includes the following steps: (1) trans-4-hydroxycyclohexylamine reacts with triphenylmethyl halide, so that triphenylmethyl-protected trans-4-hydroxycyclohexylamine shown as formula I is obtained; (2) the solution of triphenylmethyl-protected trans-4-hydroxycyclohexylamine shown as formula I is added with sodium hydride, and is then added with halogenated alkane to react, so that triphenylmethyl-protected trans-4-alkoxycyclohexylamine shown as formula II is obtained; (3) triphenylmethyl-protected trans-4-alkoxycyclohexylamine shown as formula II undergoes deprotection reaction, so that trans-4-alkoxycyclohexylamine is obtained. By utilizing the preparation method, the flow of the preparation processfor trans-4-alkoxycyclohexylamine is simpler and environmentally friendly, irritation and allergens do not exist, industrial production is easy to operate, total yield is high, and mass production iseasy.

Description

technical field [0001] The invention relates to the field of pharmaceutical intermediates, in particular to a preparation method of trans-type 4-alkoxycyclohexylamine. Background technique [0002] Trans-4-alkoxycyclohexylamine is a pharmaceutical intermediate, which can be used to produce the antidiabetic drug glimepiride. The synthetic technique of trans 4-alkoxycyclohexylamine mainly contains following 3 kinds of methods at present: [0003] The first method starts from the trans 4-hydroxycyclohexylamine, by connecting the amino group with a bisbenzyl group, then reacting with an alkyl halide to convert the hydroxyl group into an alkoxy group, and then hydrogenating to remove the bisbenzyl group to obtain the trans 4-hydroxycyclohexylamine. 4-hydroxycyclohexylamine, the reaction process is as follows: [0004] [0005] But in this route, the first step of double benzylation needs to use benzyl bromide or benzyl chloride, these two substances have great irritation and...

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): C07C213/08C07C213/06C07C215/44C07C217/52
Inventor 吴天俊
Owner SHANGHAI BALMXY PHARMA CO LTD
Who we serve
  • R&D Engineer
  • R&D Manager
  • IP Professional
Why Eureka
  • Industry Leading Data Capabilities
  • Powerful AI technology
  • Patent DNA Extraction
Social media
Try Eureka
PatSnap group products

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

© 2024 PatSnap. All rights reserved.Legal|Privacy policy|Modern Slavery Act Transparency Statement|Sitemap