【摘要】：以苯乙腈為起始原料,在氨基鈉作用下與(R)-環(huán)氧氯丙烷反應(yīng)后,經(jīng)水解、分子內(nèi)環(huán)合得(1S,5R)-1-苯基-3-氧雜二環(huán)[3,1,0]己烷-2-酮,在三氯化鋁作用下與二乙胺反應(yīng)得(1S,2R)-N,N-二乙基-2-羥甲基-1-苯基環(huán)丙烷-1-甲酰胺,再經(jīng)氯代、蓋布瑞爾反應(yīng)、氨解,最后與鹽酸成鹽得鹽酸左米那普侖,總收率25.5%(以苯乙腈計)。該工藝條件溫和、操作簡便,適合工業(yè)化生產(chǎn)。
[Abstract]:Using phenylacetonitrile as starting material, after reaction with (R)-epichlorohydrin in the action of sodium amino acid, (1S, 5R)-1-phenyl-3-oxacyclohexane-2-one was synthesized by intramolecular cyclization, and reacted with diethylamine in the action of aluminum trichloride to (1s, 2-hydroxymethyl-1-phenylcyclopropane-1-formamide), and then reacted with diethylamine in the presence of aluminum trichloride to give (1S, 2-hydroxymethyl-1-phenylcyclopropane-1-formamide), and then reacted with diethylamine under the action of aluminum trichloride to (1S, 2hydroxymethyl-1-phenylcyclopropane-1-formamide), and then reacted with diethylamine in the presence of aluminum trichloride. Levminapron hydrochloric acid was obtained by ammonia hydrolysis and salt formation with hydrochloric acid in an overall yield of 25.5% (based on phenylnitrile). The process conditions are mild, the operation is simple, and it is suitable for industrial production.
【作者單位】： 河北科技大學(xué)化學(xué)與制藥工程學(xué)院;中國醫(yī)藥工業(yè)研究總院上海醫(yī)藥工業(yè)研究院 創(chuàng)新藥物與制藥工藝國家重點實驗室;青島黃海制藥有限責任公司;
【分類號】：R914.5

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