| 第 45 卷第 4 期 |  | Vol. 45 No. 4 | | 2015 年 8 月 | Aug 2015 |
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所屬欄目：醫藥及中間體
6-氮雜-螺［3，4］辛烷鹽酸鹽的合成 |
| 胡 濤，殷躍凡
（揚子江藥業(yè)集團有限公司，江蘇 泰州 225321） |
| 摘 要：以環(huán)丁酮（1）為起始原料，與磷酰乙酸三乙酯經(jīng)Witting-Horner-Emmons反應得2-環(huán)丁烯基乙酸甲酯（2），然后與硝基甲烷經(jīng)邁克爾加成得2-（1-硝基甲基）環(huán)丁基乙酸甲酯（3），再經(jīng)氫化還原、分子內胺解得6-氮雜-螺［3，4］辛烷-7-酮（4），最后經(jīng)氫化鋁鋰還原、酸化等5步反應得到目標化合物6-氮雜-螺［3，4］辛烷鹽酸鹽，總收率為27%。其結構經(jīng)1H NMR和MS進(jìn)行確證。 |
| 關(guān)鍵詞：環(huán)丁酮；硝基甲烷；邁克爾加成；螺環(huán)化合物 |
| 中圖分類(lèi)號：TQ463 文獻標識碼：A 文章編號：1009-9212（2015）04-0036-03 |
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| Synthesis of 6-Azaspiro[3,4]octane Hydrochlorid |
| HU Tao, YIN Yue-fan
(Yangtze River Pharmaceutical Group Co., Ltd., Taizhou 225321, China) |
| Abstract：Methyl-2-cyclobutylideneacetate（2）was prepared from Witting-Horner-Emmons reaction of Cyclobutanone（1）with triethyl phosphonoacetate; a subsequent Michael addition reaction was performed to obtain methyl 2-(1-(nitromethyl)cyclobutyl)acetate（3）in the presence of nitromethane; then the methyl 2-(1-(nitromethyl)cyclobutyl)acetate（3）was hydrogenated using Raney nickel as catalyst and the followed by an intra-aminonation to give 6-azaspiro[3,4]octane-7-one（4）; the reduction of product 4 was performed using lithium aluminium hydride(AlLiH4); the subsequent acidization of the product from the reduction of 4 using hydrochoride to give the title compound 6-azaspiro[3,4]octane hydrochloride with a total 27% yield. Its structure was confirmed by 1H NMR and MS. |
| Key words：cyclobutanone; nitromethane; Michael Addition reaction; spiro compound |
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作者簡(jiǎn)介：胡 濤（1975-），男，工程師，博士，主要從事藥物合成及工藝開(kāi)發(fā)研究（E-mail：hutao@yangzijiang.com）。
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收稿日期：2015-08-03
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