Preparation method of anhydrous and non-solvation A crystallization parecoxib sodium

Abstract

The invention relates to a preparation method of anhydrous and non-solvation A crystallization parecoxib sodium. The method comprises the following steps: 1,2-phenylacetophenone and pyrrolidine are condensed to generate 1-(1,2-diphenylvinyl)pyrrolidine, then acetylation is carried out, and 4,5-dihydro-5-methyl-3,4-dibenzyl-5-isoxzzole alcohol are subjected to cyclization under sodium acetate and hydroxylamine hydrochloride. The compound is directly reacted to chlorosulfonic acid, dehydration and chlorine sulfonation reaction are carried out, and then valdecoxib can be obtained through ammonification, valdecoxib is refined, then is subjected to acetylation to obtain parecoxib, and salt forming is performed to obtain the target compound parecoxib sodium.

Description

technical field [0001] The invention relates to the technical field of chemical synthesis, in particular to a method for preparing anhydrous, non-solvated A crystal form parecoxib sodium. Background technique [0002] Parecoxib sodium has the following structural formula: [0003] [0004] It is the world's first specific cyclooxygenase-2 (COX-2) inhibitor that can be administered intravenously and intramuscularly. It is a water-soluble prodrug of valdecoxib and belongs to the coxib in anti-arthritic drugs Clinically, it is mainly used for the short-term treatment of postoperative pain, and can also be used for the treatment of moderate or severe postoperative acute pain. Compared with opioids, selective COX-2 inhibitors can effectively inhibit the expression of peripheral and central COX-2, reduce the synthesis of peripheral and central prostaglandins, inhibit hyperalgesia, increase pain threshold, and have dual analgesic advantages. The analgesic efficacy of parecoxib...

AI Technical Summary

Problems solved by technology

Its main disadvantages are: butyllithium has high chemical reactivity and high safety requirements for the reaction, which is not conducive to industrial production, and fluoride is more serious to the environment, which increases the difficulty of three wastes treatment

The main disadvantage of this method is: the reaction requires the use of more expensive reagents, such as chloroacetylation requires the use of expensive 2,6-lutidine as an acidic agent, and the reaction time is relatively long, requiring 24 hours, the reaction system It is acidic, requires high equipment, and increases production costs. At the same time, this process uses trifluoroacetic acid as a dehydration medium, which will also be affected by fluoride

The raw material of this method is more expensive, and the source of benzonitrile N oxide is limited, so this method is not suitable for industrialized production

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