Method for synthesizing benorilate by catalytically esterifying 4-dimethylamino pyridine

Abstract

The invention discloses a method for synthesizing benorilate by catalytically esterifying 4-dimethylamino pyridine, comprising the following steps of: taking the 4-dimethylamino pyridine as an ultra high-efficiency catalyst for esterifying aspirin acyl chloride and acetaminophenol; adding inorganic base as an acid catcher, wherein the mol feeding ratio of the aspirin acyl chloride to the acetaminophenol is 0.95-1.20:1.00, the mol consumption of the 4-dimethylamino pyridine is 0.05-2 percent of the acyl chloride and the mol consumption of the acid catcher is 0.5-3 times; and reacting the compounds at the temperature of 0-20DEG C for 10min to 3h to obtain the benorilate. The product quality meets the Chinese Pharmacopoeia published in 2005. The product produced by the invention has the advantages of high yield, good quality, low cost, fewer three wastes and easy control for the production.

Description

1. Technical field [0001] The invention relates to the technical field of drug synthesis, in particular to a synthesis method of benoxylate. 2. Background technology [0002] Benorylate (Benorylate) chemical name: 2-acetoxy benzoic acid p-acetamidophenyl ester, also known as parametrex, benzalole, is a non-steroidal anti-rheumatic, antipyretic and analgesic drug, a combination of aspirin and paracetamol Ester bonded lipophilic compounds. The drug has the characteristics of low gastric irritation, low toxicity and long acting time, and is widely used in clinical practice. It was approved for use in China in 1984. [0003] The existing problem of beinolate synthesis technique is: when acetylsalicyloyl chloride is directly added dropwise in the alkaline solution of the sodium hydroxide of acetaminophen, owing to there is an unstable ester group in the molecule, make partial hydrolysis and make total yield rate below 65%. In order to overcome the above shortcomings, there ha...

AI Technical Summary

Problems solved by technology

[0003] The existing problem of beinolate synthesis technique is: when acetylsalicyloyl chloride is directly added dropwise in the alkaline solution of the sodium hydroxide of acetaminophen, owing to there is an unstable ester group in the molecule, make partial hydrolysis and make total yield rate below 65%

Acetone is used as a solvent, but there are long reaction times, low yields (about 70%) and high costs. After using acetone and water as a mixed solvent, the shortcoming of long reaction times and high costs has been overcome, but the yield is higher. Low (about 65%); Add n-butyl acetate to protect acetylsalicyloyl chloride, reduce the hydrolysis of acetylsalicyloyl chloride, and significantly improve the yield to 83%. The disadvantage is that the reaction time is long

In this series of conditions, the sodium salt of acetylsalicyloyl chloride and paracetamol is more successful, using polyethylene glycol (PEG) as a phase transfer catalyst, using toluene-water as a reaction medium to obtain beinolate, but polyethylene glycol (PEG) The amount of diol and toluene is large, which brings a lot of trouble to the post-processing, which is not conducive to environmental protection.