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【结 构 式】 
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【分子编号】56146 【品名】3-(2-Chlorophenyl)propionitrile; 2-Chlorohydrocinnamonitrile 【CA登记号】 |
【 分 子 式 】C9H8ClN 【 分 子 量 】165.62196 【元素组成】C 65.27% H 4.87% Cl 21.41% N 8.46% |
合成路线1
该中间体在本合成路线中的序号：(XI)The title compound was prepared by one-pot reductive alkylation of the chiral amine (III) with 3-(2-chlorophenyl)propionitrile (XI). Reduction of nitrile (XI) by means of DIBAL at -78 C produced the intermediate diisobutylaluminium-imine complex (XII) which, after addition of (R)-3-methoxy-alpha-methylbenzylamine (III), generated imine (XIII). Subsequent reduction of imine (XIII) with NaBH4 afforded the target amine.
| 【1】 Barmore, R.M.; et al.; The addition of amines to diisobutylaluminum-imine complexes. Preparation of NPS R-568 hydrochloride. Tetrahedron Lett 1998, 39, 21, 3451. |
| 【2】 D'Ambra, T.E.; Vanwagenen, B.C.; Duff, S.R.; Nelson, W.A. (NPS Pharmaceuticals, Inc.); Method of making a benzylpropanamine. WO 9602492 . |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| (III) | 56140 | (R)-1-(3-Methoxyphenyl)ethylamine; (R)-3-Methoxy-alpha-methylbenzylamine; (R)-m-Methoxy-alpha-methylbenzylamine | 88196-70-7 | C9H13NO | 详情 | 详情 |
| (XI) | 56146 | 3-(2-Chlorophenyl)propionitrile; 2-Chlorohydrocinnamonitrile | C9H8ClN | 详情 | 详情 | |
| (XII) | 56147 | C17H27AlClN | 详情 | 详情 | ||
| (XIII) | 56148 | (1R)-N-[(E)-3-(2-chlorophenyl)propylidene]-1-(3-methoxyphenyl)-1-ethanamine; N-[(E)-3-(2-chlorophenyl)propylidene]-N-[(1R)-1-(3-methoxyphenyl)ethyl]amine | C18H20ClNO | 详情 | 详情 |
合成路线2
该中间体在本合成路线中的序号：(XI)In a different method, the primary amine (XVIII) was prepared by reduction of nitrile (XI) with either borane-dimethyl sulfide complex or with LiAlH4. Condensation of amine (XVIII) with acetophenone (I) generated imine (XIX). The asymmetric reduction of (XIX) to furnish the title (R)-amine was accomplished by using LiAlH4 in the presence of several chiral auxiliaries, such as 1,1’-binaphthol, (-)-N-methylephedrine, or (-)-N-methylpseudoephedrine, with different degrees of enantioselectivity. Alternatively, imine (XIX) was reduced utilizing a titanium-catalyzed asymmetric hydrosilylation method.
| 【1】 Buchwald, S.L.; Hansen, M.C.; Synthesis of NPS R-568 utilizing titanium-catalyzed asymmetric hydrosilylation. Tetrahedron Lett 1999, 40, 11, 2033. |
| 【2】 Van Wagenen, B.C.; Barmore, R.M. (NPS Pharmaceuticals, Inc.); Chiral reductions of imines leading to the syntheses of optically active amines. WO 9711934 . |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| (I) | 18792 | 3-methoxyacetophenone; 1-(3-methoxyphenyl)-1-ethanone | 586-37-8 | C9H10O2 | 详情 | 详情 |
| (XI) | 56146 | 3-(2-Chlorophenyl)propionitrile; 2-Chlorohydrocinnamonitrile | C9H8ClN | 详情 | 详情 | |
| (XVIII) | 56152 | 3-(2-chlorophenyl)-1-propanamine; 3-(2-chlorophenyl)propylamine | C9H12ClN | 详情 | 详情 | |
| (XIX) | 56153 | 3-(2-chlorophenyl)-N-[(E)-1-(3-methoxyphenyl)ethylidene]-1-propanamine; N-[3-(2-chlorophenyl)propyl]-N-[(E)-1-(3-methoxyphenyl)ethylidene]amine | C18H20ClNO | 详情 | 详情 |