| 第 50 卷第 6 期 |  | Vol. 50 No. 6 | | 2020 年 12 月 | Dec 2020 |
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所屬欄目：醫藥及中間體
（2S）-N-二苯甲基-2-吡咯甲酰胺的合成工藝優(yōu)化 |
| 鄧護軍，王軍緒，付國兵，張 寧，梁春梅
（西安萬(wàn)隆制藥股份有限公司，陜西 西安 710119） |
| 摘 要：以廉價(jià)易得的二苯甲醇為起始物料，依次經(jīng)氯化、氨解、酰胺化3步反應合成了（2S）-N-二苯甲基-2-吡咯甲酰胺。優(yōu)化的工藝條件為：氯化反應以氯化亞砜作氯源；氨解反應純化溶劑n（乙酸乙酯）∶n（異丙醇）=1∶3、打漿溫度10~20 ℃；酰胺化反應時(shí)間3 h。優(yōu)化后的反應總收率65.3%，產(chǎn)品純度98.5%。合成路線(xiàn)簡(jiǎn)便，工藝穩定。 |
| 關(guān)鍵詞：（2S）-N-二苯甲基-2-吡咯甲酰胺；二苯氯甲烷；工藝優(yōu)化 |
| 中圖分類(lèi)號：R914 文獻標識碼：A 文章編號：1009-9212（2020）06-0041-04 |
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| The Optimization of Synthesis Process of (2S)-N-Diphenylmethyl-2-pyrrolidinecarboxamide |
| DENG Hu-jun, WANG Jun-xu, FU Guo-bing, ZHANG Ning, LIANG Chun-mei
(Xi'an WanLong Pharmaceutical Co., Ltd., Xi'an 710119, China) |
| Abstract：The pharmaceutical intermediate, (2S)-N-diphenylmethyl-2-pyrrolidinecarboxamide, was synthesized through a series of reactions including chlorination, ammonolysis, and amidation with using commercialized diphenylmethanol as the starting material. The main factors influencing the reactions were investigated. The experimental results showed that: using thionyl chloride as chlorine source, the solvent molar ratio of ethyl acetate to isopropyl alcohol is 1∶3, and the purification temperature is 10~20 ℃, the amidation time is 3 h. The overall yield amounts to 65.3% and the purity reached 98.5%. The route has mild reaction conditions and simple operation, and is suitable for industrial scale production． |
| Key words：(2S)-N-diphenylmethyl 2-pyrrolidinecarboxamide; chlorodiphenylmethane; process optimization |
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基金項目：陜西省自然科學(xué)基礎研究計劃（面上）（2018JM7046）。
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作者簡(jiǎn)介：鄧護軍（1969—），男，陜西西安人，工程師，主要從事藥物合成與研發(fā)。
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收稿日期：2020-11-09
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