Synthetic preparation method of paracetamol

Abstract

The synthetic preparation method comprises the following steps: adding acetylsalicylic acid and a Vilsmeier reagent into an organic solvent, and carrying out complete stirring reaction at the temperature of 0-70 DEG C under the catalysis of an acid-binding agent to generate acetylsalicylic acid acyl chloride; the acetylsalicylic acid acyl chloride is dropwise added into the paracetamol sodium salt solution, the temperature is controlled to be 8-12 DEG C, the pH value of the solution is controlled to be 8-10, crystallization is conducted for 0.5-2.0 h, and the paracetamol is obtained. According to the invention, BTC and DMF are adopted to react to generate a Vilsmeier reagent, and compared with liquid chlorinated reagents such as thionyl chloride and oxalyl chloride, the usage amount is small, the pungent smell is small, and the production process is safer; meanwhile, BTC and DMF react to generate a Vilsmeier reagent, the Vilsmeier reagent is used as a chlorination reagent for chlorination reaction, and the smell is small in the production process; the using amount of BTC is 40% of that of BTC which is directly used, the using amount is greatly reduced, meanwhile, the amount of generated wastewater is reduced, environmental pollution is reduced, meanwhile, the difficulty of wastewater environment-friendly treatment is reduced, and the method is more environmentally friendly.

Description

technical field [0001] The invention belongs to the field of synthesizing fluotacin, in particular to a synthesis and preparation method of flutoid pain and a preparation method thereof. Background technique [0002] Benorilate (Benorilate), also known as benolalai, benolate, scientific name 2-acetoxybenzoic acid-4-acetamidophenyl ester, is an esterified prodrug formed by combining the chemical structures of acetaminophen and aspirin , which belongs to non-steroidal anti-inflammatory antipyretic analgesics, clinically produces analgesic, anti-inflammatory and antipyretic effects mainly by inhibiting the synthesis of prostaglandins. Because beinolate has the characteristics of little gastric irritation, low toxicity and long duration of action, it is widely used clinically. [0003] There are mainly two kinds of preparation methods of existing parametacin, one preparation method is direct synthesis (Journal of Sichuan Agricultural University, 2016, 34 (1): 110-114 and other ...

AI Technical Summary

Problems solved by technology

In industrial production, the first step, in the reaction process that acetylsalicylic acid generates acid chloride, existing technology generally uses liquid chlorination reagents such as thionyl chloride, oxalyl chloride (Chinese Journal of Pharmaceutical Industry, 1995, 26 (12 ), 532-533; Journal of Guiyang Medical College, 2012, 37(4), 440-443; documents such as CN201710044016.6), during the chlorination reaction, the chlorination reagent is also used as a solvent for the chlorination reaction, and the feeding amount Largely excessive, not only strong pungent odor is produced in the production process, but also a large amount of toxic and harmful gases such as HCl and SO2, a large amount of waste water, and serious environmental pollution; with the development of technology, there are also some methods to use solid triphosgene as chlorinated Reagents (CN200910117289.4, CN201010517633.1 and other documents), the direct use of solid triphosgene requires more than 1.0 times the equivalent, will produce more than 3 times the equivalent of hydrochloric acid, generate a large amount of waste water, thereby increasing environmental protection costs