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【结 构 式】 
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【分子编号】24061 【品名】3-methoxyphenylacetonitrile; 2-(3-methoxyphenyl)acetonitrile 【CA登记号】19924-43-7 |
【 分 子 式 】C9H9NO 【 分 子 量 】147.1766 【元素组成】C 73.45% H 6.16% N 9.52% O 10.87% |
合成路线1
该中间体在本合成路线中的序号：(III)By condensation of 2-(3-methoxyphenyl)tetradecanenitrile (I) [prepared by alkylation of 3-methoxyphenylacetonitrile (III) with 1-bromoundecane (IV) with 1-chloro-4-methyl-6-(3-methoxyphenyl)-4-azahexane (II) (prepared by alkylation of N-methyl-[2-(3-methoxyphenyl)ethylamine (VI) with 1-bromo-3-chloropropane (V)) by means of sodium amide in refluxing toluene.
| 【1】 Ehrmann, O.; et al. (BASF AG); omega-Cyano-1, omega-diphenyl-azaalkiane derivatives, their preparation and drugs containing them. DE 3144150 . |
| 【2】 Castaner, J.; Prous, J.; Anipamil. Drugs Fut 1986, 11, 3, 171. |
| 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) | 24059 | 2-(3-methoxyphenyl)tetradecanenitrile | C21H33NO | 详情 | 详情 | |
| (II) | 24060 | 3-chloro-N-(3-methoxyphenethyl)-N-methyl-1-propanamine | C13H20ClNO | 详情 | 详情 | |
| (III) | 24061 | 3-methoxyphenylacetonitrile; 2-(3-methoxyphenyl)acetonitrile | 19924-43-7 | C9H9NO | 详情 | 详情 |
| (IV) | 24062 | 1-bromododecane | 143-15-7 | C12H25Br | 详情 | 详情 |
| (V) | 10358 | 1-Bromo-3-chloropropane | 109-70-6 | C3H6BrCl | 详情 | 详情 |
| (VI) | 24064 | 2-(3-methoxyphenyl)-N-methyl-1-ethanamine | C10H15NO | 详情 | 详情 |
合成路线2
该中间体在本合成路线中的序号：(VIII)The condensation of (3-methoxyphenyl)acetonitrile (VIII) with 3-bromopropyltetrahydropyranyl ether (IX) by means of lithium diisopropylamide in THF gives 2-(3-methoxyphenyl)-5-tetrahydropyranyloxypentanonitrile (X), which is oxidized with chromic anhydride-H2SO4 yielding 4-cyano-3-(3-methoxyphenyl)butyric acid (XI). The hydrolysis of (XI) with KOH in ethanol-water affords 2-(3-methoxyphenyl)glutaric acid (XII), which is anhydrized with refluxing acetic anhydride giving 2-(3-methoxyphenyl)glutaric anhydride (XIII). The reaction of (XIII) with propylamine (C) in refluxing benzene yields 2-(3-methoxyphenyl)-N-propylglutarimide (XIV), which is demethylated with BBr3 in methylene chloride to 2-(3-hydroxyphenyl)-N-propylglutarimide (XV). The benzylation of (XV) with benzyl bromide and K2CO3 in DMF affords 2-(3-benzyloxyphenyl)-N-propylglutarimide (XVI), which is reduced with LiAlH4 in THF giving 3-(3-benzyloxyphenyl)-N-propylpiperidine (XVII). Finally, this compound is debenzylated by hydrogenolysis with H2 over Pd/C in AcOH.
| 【1】 Brands, F.T.L.; Loozen, H.J.J.; An efficient synthesis of 3-arylpiperidines. J R Neth Chem Soc 1981, 100, 9, 333-336. |
| 【2】 Serradell, M.N.; Nohria, V.; Castaner, J.; Blancafort, P.; 3-PPP. Drugs Fut 1983, 8, 1, 27. |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| 12912 | 1-(Bromomethyl)benzene; Alpha-bromotoluene | 100-39-0 | C7H7Br | 详情 | 详情 | |
| (VIII) | 24061 | 3-methoxyphenylacetonitrile; 2-(3-methoxyphenyl)acetonitrile | 19924-43-7 | C9H9NO | 详情 | 详情 |
| (IX) | 29460 | 2-(4-bromobutoxy)tetrahydro-2H-pyran; 4-bromobutyl tetrahydro-2H-pyran-2-yl ether | C9H17BrO2 | 详情 | 详情 | |
| (X) | 35989 | 2-(3-methoxyphenyl)-6-(tetrahydro-2H-pyran-2-yloxy)hexanenitrile | C18H25NO3 | 详情 | 详情 | |
| (XI) | 35990 | 4-cyano-4-(3-methoxyphenyl)butyric acid | C12H13NO3 | 详情 | 详情 | |
| (XII) | 35991 | 2-(3-methoxyphenyl)pentanedioic acid | C12H14O5 | 详情 | 详情 | |
| (XIII) | 35992 | 3-(3-methoxyphenyl)dihydro-2H-pyran-2,6(3H)-dione | C12H12O4 | 详情 | 详情 | |
| (XIV) | 35993 | 3-(3-methoxyphenyl)-1-propyl-2,6-piperidinedione | C15H19NO3 | 详情 | 详情 | |
| (XV) | 35994 | 3-(3-hydroxyphenyl)-1-propyl-2,6-piperidinedione | C14H17NO3 | 详情 | 详情 | |
| (XVI) | 35995 | 3-[3-(benzyloxy)phenyl]-1-propyl-2,6-piperidinedione | C21H23NO3 | 详情 | 详情 | |
| (XVII) | 35996 | benzyl 3-(1-propyl-3-piperidinyl)phenyl ether; 3-[3-(benzyloxy)phenyl]-1-propylpiperidine | C21H27NO | 详情 | 详情 | |
| (C) | 23923 | 1-propanamine | 107-10-8 | C3H9N | 详情 | 详情 |