| 第 46 卷第 2 期 |  | Vol. 46 No. 2 | | 2016 年 4 月 | Apr 2016 |
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所屬欄目：醫藥及中間體
2-氨基-3-（1-金剛烷基）丙酸鹽酸鹽的合成 |
| 胡 濤，殷躍凡，張海波
（揚子江藥業(yè)集團有限公司，江蘇 泰州 225321） |
| 摘 要：以1-金剛烷甲醇（1）為起始原料，經(jīng)PCC氧化得1-金剛烷甲醛（2），隨后經(jīng)維悌希反應引入醛基得2-（1-金剛烷基）乙醛（3）、經(jīng)與芐胺、氰基三甲基硅烷通過(guò)改進(jìn)的斯特雷克反應一鍋法生成α氨基腈（4）、再經(jīng)水解成酰胺（5），脫去芐基得到α氨基酰胺（6）、最后在鹽酸作用下水解成鹽得標題化合物2-氨基-3-（1-金剛烷基）丙酸鹽酸鹽（TM），共6步反應，總收率為23%，其結構經(jīng)1H NMR和MS進(jìn)行確證。 |
| 關(guān)鍵詞：金剛烷甲醇；維悌希反應；氰基三甲基硅烷；斯特雷克反應；一鍋法 |
| 中圖分類(lèi)號：TQ463 文獻標識碼：A 文章編號：1009-9212（2015）06-0035-04 |
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| Synthesis of 3-(Adamantan-1-yl)-2-aminopropanoic Acid Hydrochloride |
| HU Tao, YIN Yue-fan, ZHANG Hai-bo
(Yangtze River Pharmaceutical Group Co., Ltd., Taizhou 225321, China) |
| Abstract：Using PCC as the catalyst, (adamantan-1-yl)methanol(1)was oxidized into adamantane-1-carbaldehyde(2) and then 2-(adamantan-1-yl)acetaldehyde(3) was obtained via Witting reaction of 2 with (methoxymethyl)triphenylphodphonium chloride. α-Aminonitrile(4) was obtained through an improved one-pot Strecker reaction of 3 with benzylamine and trimethylsilanecarbonitrile. α-Aminoamide (6) was obtained through a series of reactions of 4 including hydrolysis, de-benzyl via hydrogenolysis catalyzed by Palladium/carbon. Finally, the title compound, 3-(adamantan-1-yl)-2-aminopropanoic acid hydrochloride was produced by the acidic hydrolysis of 6 using hydrochloride acid with a total yield of 23% and its structure was confirmed by 1H NMR and MS. |
| Key words：(adamantan-1-yl)methanol; witting reaction; trimethylsilanecarbonitrile; strecker reaction; one-pot |
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作者簡(jiǎn)介：胡 濤（1975-），男，河南信陽(yáng)人，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： 2016-04-0
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