Preparation method of benzo[1,3-d]dioxole and its intermediate

A dioxole, 3-d technology, applied in the direction of organic chemistry, bulk chemical production, etc., can solve the problems of low overall yield, unsuitable for industrial production, dangerous sodium cyanide reagent, etc., and shorten the reaction route. , the effect of improving the overall yield of the reaction
CN106749156BActive Publication Date: 2020-04-10ZHEJIANG YONGNING PHARMA
5 Cites 0 Cited by

Patent Information

Authority / Receiving Office
CN · China
Patent Type
Patents(China)
Current Assignee / Owner
ZHEJIANG YONGNING PHARMA
Publication Date
2020-04-10

Smart Images

  • Figure 1
    Figure 1
  • Figure 2
    Figure 2
  • Figure 3
    Figure 3
Patent Text Reader

Abstract

The invention relates to the field of medicinal chemical synthesis, and discloses a method for preparing benzo[1,3-d] dioxole and an intermediate of benzo[1,3-d] dioxole. The method comprises the following steps: performing three steps of reactions of chloro-substitution, fluorination and deprotection on a compound of formula (4) as shown in the specification so as to prepare a compound of formula (1) as shown in the specification, and in the formulae, R is a carboxyl protection group. By adopting the method, the problems that in the prior art, the yield of benzo[1,3-d] dioxole is low and the reaction operation is not safe can be solved, the compound of the formula (4) is adopted as a raw material which is directly introduced into a three-membered ring structure, so that a dangerous sodium cyanide reagent is not used, and moreover, a reaction route is shortened, the overall yield of the reaction can be greatly increased, and the method is applicable to industrial production.
Need to check novelty before this filing date? Find Prior Art

Description

technical field

[0001] The invention belongs to the field of pharmaceutical chemical synthesis, and in particular relates to a preparation method of benzo[1,3-d]dioxole and an intermediate thereof. Background technique

[0002] Lumacaftor is a CFTR modulator developed by Vertex Pharmaceuticals and approved for the treatment of cystic fibrosis. Its structural formula is as follows:

[0003]

[0004] In the preparation process of a series of CFTR modulators such as lumacaftor, benzo[1,3-d]dioxole represented by formula (1) is a key intermediate:

[0005]

[0006] Patent CN101356170 discloses the preparation of benzo[1,3- d] the method of dioxole, concrete route is as follows:

[0007]

[0008] There are following defects in this route: 1. the reaction raw materials are expensive, which is unfavorable for cost control; 2. palladium catalyst is used in the reaction process, and palladium residues are easily arranged in the product; 3. the sodium cyanide reagent used ...

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