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【结 构 式】 
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【分子编号】41699 【品名】(E)-3-(3,4-dimethylphenyl)-2-propenenitrile 【CA登记号】 |
【 分 子 式 】C11H11N 【 分 子 量 】157.21508 【元素组成】C 84.04% H 7.05% N 8.91% |
合成路线1
该中间体在本合成路线中的序号：(VII)The 2-chloroethylation of ethyl homovanillate (I) with 1-bromo-2-chloroethane and K2CO3 in acetone gives ethyl 2-[4-(2-chloroethoxy)-3-methoxyphenyl]acetate (II), which is treated with sodium azide in toluene followed by hydrolysis with aqueous NaOH in MeOH, yielding 2-[4-(2-azidoethoxy)-3-methoxyphenyl]acetic acid (IV). The reaction of (IV) with SOCl2 and Et3N affords the acyl chloride (V). The reaction of 3-iodo-o-xylene (VI) and acrylonitrile under the Heck reaction conditions [Pd(OAc)2, tri-o-tolylphosphine and Et3N in MeCN] gives an isomeric mixture of 3-(3,4-dimethyl-phenyl)-2-propenenitrile (VII), which is hydrogenated with Pd/C followed by Raney-Ni to provide 3-(3,4-dimethylphenyl)propylamine (IX). The coupling reaction between the acyl chloride (V) and amine (IX) with Et3N in CH2Cl2 gives the amide (X). Finally, Pd/C catalyzed hydrogenation of this compound affords 2-[4-(2-aminoethoxy)-3-methoxyphenyl]-N-[3-(3,4-dimethylphenyl)propyl]acetamide.
| 【1】 Lee, C.W.; Park, N.S.; Seong, C.M.; Jung, Y.S.; Baek, G.H.; Cho, S.J.; Synthesis of 3-arylpropylamine derivatives from aryl halides using Heck reaction. Bull Korean Chem Soc 1999, 20, 232-236. |
| 【2】 Park, N.S.; Kim, W.B.; Kim, S.H.; Seong, C.M.; Jung, Y.S.; DA-5018. Drugs Fut 2000, 25, 11, 1131. |
| 【3】 Lee, K.S.; Choi, J.K.; Hong, M.S.; Kim, H.S.; Lim, H.J.; Ha, D.C.; Park, N.S. (Korea Research Institute of Chemical Technology); Novel phenylacetamide derivs. and processes for the preparation thereof. EP 0525360; US 5242944 . |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| 10847 | Acrylonitrile | 107-13-1 | C3H3N | 详情 | 详情 | |
| (I) | 41693 | ethyl 2-(4-hydroxy-3-methoxyphenyl)acetate | C11H14O4 | 详情 | 详情 | |
| (II) | 41694 | ethyl 2-[4-(2-chloroethoxy)-3-methoxyphenyl]acetate | C13H17ClO4 | 详情 | 详情 | |
| (III) | 41695 | ethyl 2-[4-(2-azidoethoxy)-3-methoxyphenyl]acetate | C13H17N3O4 | 详情 | 详情 | |
| (IV) | 41696 | 2-[4-(2-azidoethoxy)-3-methoxyphenyl]acetic acid | C11H13N3O4 | 详情 | 详情 | |
| (V) | 41697 | 2-[4-(2-azidoethoxy)-3-methoxyphenyl]acetyl chloride | C11H12ClN3O3 | 详情 | 详情 | |
| (VI) | 41698 | 4-iodo-1,2-dimethylbenzene | 31599-61-8 | C8H9I | 详情 | 详情 |
| (VII) | 41699 | (E)-3-(3,4-dimethylphenyl)-2-propenenitrile | C11H11N | 详情 | 详情 | |
| (VIII) | 41700 | 3-(3,4-dimethylphenyl)propanenitrile | C11H13N | 详情 | 详情 | |
| (IX) | 40288 | 3-(3,4-dimethylphenyl)-1-propanamine; 3-(3,4-dimethylphenyl)propylamine | C11H17N | 详情 | 详情 | |
| (X) | 40292 | 2-[4-(2-azidoethoxy)-3-methoxyphenyl]-N-[3-(3,4-dimethylphenyl)propyl]acetamide | C22H28N4O3 | 详情 | 详情 |