Method for preparing Vilanterol

A technology of tetrahydrofuran and reaction solvent, which is applied in the field of preparation of vilanterol, can solve the problems of difficulty in meeting the quality requirements of chiral purity, difficulty in constructing chiral centers, and restrictions on industrial applications, so as to avoid the use of protective groups and increase the utilization of atoms The effect of low production rate and production cost

Active Publication Date: 2019-04-05
ANHUI DEXINJIA BIOPHARM
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  • Abstract
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Problems solved by technology

But this route synthesis step is longer, wherein needs to use a plurality of protecting groups, functional group protection and deprotection have increased reaction steps, and wherein also use bis (tert-butoxycarbonyl) amine to remove a tert-butoxycarbonyl again, The low utilization rate of atoms leads to low synthesis yield, which limits its industrial application, and the construction of chiral centers is difficult, and the chiral purity meets the quality requirements.

Method used

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  • Method for preparing Vilanterol
  • Method for preparing Vilanterol
  • Method for preparing Vilanterol

Examples

Experimental program
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Embodiment 1

[0023] Preparation of Intermediate 1:

[0024] Add 200mL water to a 500mL three-necked flask, add 13.2g (1.1eq) sodium hydroxide in batches, cool to 0-5°C, add 37.2g (1eq) salicyl alcohol while stirring, and then add 0.68g (1%) Benzyltriethylammonium chloride, fully stirred for 1 hour, under the condition of 0-5 ℃, slowly added 44.4g of 50% glyoxylic acid aqueous solution into the reaction system dropwise within 1 hour, and the temperature of the reaction system rose to 25 ℃, continue to react for 6 hours, and the remaining raw materials in the liquid phase are less than 1%, and the reaction is completed. Cool the system to 0-5°C, adjust the pH to 2-3 with concentrated hydrochloric acid, extract with 100×2 mL of tert-butyl acetate, combine the organic phases, wash with 100 mL of saturated saline and 100 mL of water, dry over anhydrous magnesium sulfate, and filter. Concentration gave a white solid, and the crude product was recrystallized from toluene to obtain 50 g, with a y...

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Abstract

The invention discloses a method for preparing Vilanterol, and belongs to the field of drug synthesis. The method includes the steps: (1) performing addition reaction on salicyloyl and glyoxylic acidto generate an intermediate 1; (2) performing chiral resolution on the intermediate 1 to obtain a chiral intermediate 2; (3) performing acylation reaction on the intermediate 2 and an intermediate 3 to generate an intermediate 4; (4) reducing the intermediate 4 to obtain the Vilanterol. The intermediate 3 is obtained by performing Darebin reaction on an intermediate 5. Raw materials are easily obtained, a synthetic route is short, production cost is reduced, reaction conditions are mild, and the method is simple in operation and suitable for industrial production.

Description

technical field [0001] The invention belongs to the field of drug synthesis and relates to a method for preparing vilanterol. Background technique [0002] Vilanterol trifenatate (Vilanterol trifenatate) is a long-acting beta 2 receptor agonists. Its compound preparation with fluticasone furoate and its compound preparation with umeclidinium bromide were approved by FDA in May and December 2013, respectively, for the treatment of obstructive pulmonary disease and asthma. The molecular weight of vilanterol is 486.4, the molecular formula is C24H33Cl2NO5, CAS: 503068-34-6, the Chinese name is: chemical name: (R)-4-[2-[[6-[(2,6-dichlorobenzyl )oxyl]-ethoxyl]ethyl]amino]-1-hydroxyethyl]-2-hydroxyethyl]-2-hydroxymethylphenol, the chemical structural formula is as shown: [0003] [0004] The world patent WO2003024439 relates to a method for synthesizing vilanterol, the specific synthetic route is as follows: [0005] [0006] This synthetic route is the original researc...

Claims

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Application Information

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IPC IPC(8): C07C213/02C07C217/08C07C231/02C07C235/34C07C51/367C07C51/487C07C59/52C07B57/00
CPCC07B57/00C07B2200/07C07C51/367C07C51/487C07C213/02C07C231/02C07C217/08C07C235/34C07C59/52
Inventor 张启龙许坤郑庚修高令峰诸葛文云
Owner ANHUI DEXINJIA BIOPHARM
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