Unlock instant, AI-driven research and patent intelligence for your innovation.

A kind of preparation method of 2,2-difluoro-5-chloromethyl piperonyl ring

The technology of chloromethyl piperonyl ring and difluoro piperonyl ring is applied in the field of preparation of 2,2-difluoro-5-chloromethyl piperonyl ring, can solve the problems of serious reaction pollution, difficult operation and high reaction cost, and achieves The effect of low reaction cost, simple post-processing and high yield

Active Publication Date: 2017-09-15
安庆融创生物科技有限公司
View PDF3 Cites 0 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0006] The purpose of the present invention is to overcome the problems of high reaction cost, difficult operation and serious reaction pollution in the above preparation method in industrialization, and provide a 2,2-difluoro-5- The preparation method of chloromethyl piperonyl ring

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
  • A kind of preparation method of 2,2-difluoro-5-chloromethyl piperonyl ring
  • A kind of preparation method of 2,2-difluoro-5-chloromethyl piperonyl ring
  • A kind of preparation method of 2,2-difluoro-5-chloromethyl piperonyl ring

Examples

Experimental program
Comparison scheme
Effect test

preparation example Construction

[0021] The present invention provides a kind of preparation method of 2,2-difluoro-5-chloromethyl piperonyl ring, comprising the following steps:

[0022] 2,2-Difluoropiperone ring (Ⅰ) (English name: 2,2-difluorobenzo[d][1,3]dioxole) and chloromethyl ether undergo chloromethylation under the catalysis of Lewis acid to obtain 2,2-Difluoro-5-chloromethyl piperonyl ring (Ⅱ) (English name, 5-(chloromethyl)-2,2-difluorobenzo[d][1,3]dioxole), its reaction equation is as follows:

[0023]

[0024] The specific method of the reaction is as follows: adding 2,2-difluoropiperonyl, chloromethyl ether and Lewis acid into a reaction vessel for reaction.

[0025] The catalyst Lewis acid can be added to the reaction vessel at one time or in batches. Lewis acids that can be used include, but are not limited to, anhydrous zinc dichloride, anhydrous aluminum trichloride, anhydrous ferric chloride, tin tetrachloride, titanium tetrachloride or boron trifluoride etherate or multiple combinatio...

Embodiment 1

[0034] Add 2,2-difluoro-5-chloromethyl piperonyl (10g, 0.063mol), chloromethyl methyl ether (105ml, 1.386mol), 100ml dichloromethane, anhydrous zinc dichloride to the reaction flask respectively (17.2g, 0.126mol), reacted at room temperature for 3 hours, and the reaction was complete by TLC monitoring. Pour the reaction solution into 500ml of ice water, stir for 10 minutes, extract 100ml x 3 times with dichloromethane, combine the organic phases, wash with 200ml x 3 of water, wash with 350ml of saturated saline, dry, and spin dry to obtain 2,2-difluoro - 15 grams of light yellow oily substance of 5-chloromethyl piperonylcycline. Distilled under reduced pressure and received the fraction at 70-74°C under 0.5mmHg to obtain 11.7g of product with an isolated yield of 90%. The purity of the product before distillation: the purity detected by TLC is more than 90%, and the purity detected by lcms is: 90.41% (Agilent 1200).

[0035] 1 H NMR (400 MHz, DMSO) δ 7.42 (s, 1H), 7.32 (d, ...

Embodiment 2

[0037] Example 2: Preparation of 2,2-difluoro-5-chloromethyl piperonyl ring

[0038] With embodiment 1, just catalyzer is anhydrous aluminum trichloride, and the isolated yield of product is 70%.

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 relates to the field of organic synthesis, in particular to a preparation method of 2,2-difluoro-5-chloromethyl benzodioxole. The method includes the step that 2,2-difluoro benzodioxole (I) and chloro-methyl ether are subjected to a chloromethylation reaction under the catalytic action of lewis acid to obtain 2,2-difluoro-5-chloromethyl benzodioxole (II), wherein the reaction equation is shown in the specification. Difluoro benzodioxole which is cheap and easy to get is adopted as the raw material, and 2,2-difluoro-5-chloromethyl benzodioxole is obtained through one-step reaction. The reaction conditions are mild, the yield is high, waste gas pollution is reduced, after-treatment is simple, the reaction cost is low, and the preparation method is suitable for industrial production.

Description

technical field [0001] The invention relates to the field of organic synthesis, in particular to a preparation method of 2,2-difluoro-5-chloromethyl piperonylcycline. Background technique [0002] 2,2-Difluoro-5-chloromethyl piperonyl ring is an important intermediate, mainly used as pharmaceutical intermediates, organic synthesis intermediates, etc. [0003] In the existing synthetic method (WO2011127241), the reaction equation is as follows: [0004] [0005] This route uses 2,2-difluoro-5-carboxypiperone as a raw material and is synthesized in two steps. The starting material is not available in the market and is expensive, which is not conducive to mass production in the market. In addition, LAH reduction is used in the reaction process, which has high operational risks and high requirements for equipment. In the second step, thionyl chloride is used for chlorination, which produces a large amount of hydrogen chloride gas, serious pollution of acid water, tail gas, a...

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): C07D317/46
CPCC07D317/46
Inventor 赵开全王晓辉
Owner 安庆融创生物科技有限公司