Study On The Synthesis Of Phenylpiracetam

Phenylpiracetam,commonly known as carphedon,is a central nervous system drug that can promote cognitive ability and enhance memory.It is believed that the drug can increase the energy supply of brain cells,enhance the activity of brain cells,promote brain metabolism and blood circulation,and selectively act on the nerve pathways related to learning and memory in the brain,thus improving the learning and memory function.The drug has obvious recovery and improvement effect on senile dementia disease,so it has received extensive attention.In this paper,the general situation of senile dementia disease and the drugs used to treat it were briefly introduced.The synthetic methods of phenylpiracetam and4-phenyl-2-pyrrolidone,an important intermediate,were reviewed.Through theoretical analysis and research,the synthetic process of phenylpiracetam was designed.Two synthetic routes were used to synthesize the intermediate 4-phenyl-2-pyrrolidone.The first route is to use phenylacetonitrile as raw material and anhydrous potassium carbonate as catalyst to produce ethyl 3-cyano-3-phenylpropanoic acid ethyl ester by nucleophilic substitution reaction with ethyl chloroacetate in 90.60%yield.Then,the intermediate4-phenyl-2-pyrrolidone was synthesized by hydrogenation of ethyl3-cyano-3-phenylpropanoic acid ethyl ester to cyano with nickel as catalyst,and the yield was 89%.This route avoids the use of strong alkali such as sodium hydride,avoids the production of hydrogen,and the products of catalytic hydrogenation reduction are closed in a high-pressure autoclave,thus shortening the three-step reaction to two-step operation.The second route is to use 4-amino-3-phenylbutyric acid hydrochloride as raw material,methanol as solvent,concentrated sulfuric acid as catalyst and methanol to react to produce methyl 4-amino-3-phenylbutyrate,adding triethylamine to neutralize hydrochloric acid and catalyst,then heating to produce urethane exchange,cyclization to intermediate4-phenyl-2-pyrrolidone,the yield is 94.08%,the reaction is simple and the yield is high.Subsequently,4-phenyl-2-pyrrolidone reacted with ethyl bromoacetate under the action of sodium hydride to produce ethyl 2-oxo-4-phenyl-1-pyrrolidine acetate with a yield of90.02%.Finally,ethyl 2-oxo-4-phenyl-1-pyrrolidine acetate and ammonia water were transesterified to produce phenylpiracetam in 93.34%yield.Through single factor experiments,the key factors affecting the above reaction were studied,and the optimum technological conditions were obtained.The total yields of the two routes were 67.74%and70.58%,respectively.The products and intermediates were characterized and analyzed by IR and ~1H NMR.