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【结 构 式】 
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【分子编号】58594 【品名】N-[(1S,4S)-4-(3,4-dichlorophenyl)-1,2,3,4-tetrahydro-1-naphthalenyl]-N-methylamine; (1S,4S)-4-(3,4-dichlorophenyl)-N-methyl-1,2,3,4-tetrahydro-1-naphthalenamine 【CA登记号】 |
【 分 子 式 】C17H17Cl2N 【 分 子 量 】306.23412 【元素组成】C 66.68% H 5.6% Cl 23.15% N 4.57% |
合成路线1
该中间体在本合成路线中的序号：(VI)The condensation of 1-naphthol (I) with an excess of o-dichlorobenzene (II) at 100 C by means of anhydrous AlCl3 gives 4-(3,4-dichlorophenyl)-1-tetralone (III), which is allowed to react with N-methylhydroxylamine (IV) and NaOAc in refluxing ethanol, yielding the nitrone (V). The reduction of (V) with H2 over RaNi in methanol affords a racemic cis/trans (9:1) mixture of methylamines, which by crystallization of its hydrochloride in ethanol provides pure (racemic)-(cis)-(VI). Finally, the target (1S)-(cis)-compound is obtained by optical resolution of (VI) with (R)-(-)-mandelic acid.
| 【1】 Vukics, K.; et al.; Improved industrial synthesis of antidepressant sertraline. Org Process Res Dev 2002, 6, 1, 82. |
| 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) | 22935 | alpha-naphthol; 1-naphthol | 90-15-3 | C10H8O | 详情 | 详情 |
| (II) | 58592 | 1,2-Dichlorobenzene; chloroben; chloroden; cloroben; Dichloricide; Dichlorobenzol; dilantin db; dilatin db; dizene; dowtherm e; o-Dichlorobenzene; o-Dichlorobenzol; termitkil | 95-50-1 | C6H4Cl2 | 详情 | 详情 |
| (III) | 30583 | 4-(3,4-dichlorophenyl)-3,4-dihydro-1(2H)-naphthalenone; 4-(3',4'-Dichlorophenyl)-1-tetralone | 79580-19-3 | C16H12Cl2O | 详情 | 详情 |
| (IV) | 12690 | (Hydroxyamino)methane; N-Methylhydroxylamine | 593-77-1 | CH5NO | 详情 | 详情 |
| (V) | 58593 | [4-(3,4-dichlorophenyl)-3,4-dihydro-1(2H)-naphthalenylidene](methyl)ammoniumolate | C17H15Cl2NO | 详情 | 详情 | |
| (VI) | 58594 | N-[(1S,4S)-4-(3,4-dichlorophenyl)-1,2,3,4-tetrahydro-1-naphthalenyl]-N-methylamine; (1S,4S)-4-(3,4-dichlorophenyl)-N-methyl-1,2,3,4-tetrahydro-1-naphthalenamine | C17H17Cl2N | 详情 | 详情 |
合成路线2
该中间体在本合成路线中的序号：(rac)-(cis)-(III)The reaction of 4-(3,4-dichlorophenyl)-1,2,3,4-tetrahydronaphthalen-1-one (I) with methylamine and formic acid in DMF gives the corresponding methylimine (II), which is reduced with H2 over Pd/C to yield (rac)(cis)-4-(3,4-dichlorophenyl)-N-methyl-1,2,3,4-tetrahydronaphthalen-1-amine (rac)(cis)(III). Finally, this compound is submitted to optical resolution by means of mandelic acid to afford the target (1S)(cis)-sertraline.
| 【1】 Laitinen, I.; Pietikaeinen, P. (Orion Corporation); Process for the production of sertraline and intermediates useful therefor. US 2003013768 . |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| (rac)-(cis)-(III) | 58594 | N-[(1S,4S)-4-(3,4-dichlorophenyl)-1,2,3,4-tetrahydro-1-naphthalenyl]-N-methylamine; (1S,4S)-4-(3,4-dichlorophenyl)-N-methyl-1,2,3,4-tetrahydro-1-naphthalenamine | C17H17Cl2N | 详情 | 详情 | |
| (I) | 30583 | 4-(3,4-dichlorophenyl)-3,4-dihydro-1(2H)-naphthalenone; 4-(3',4'-Dichlorophenyl)-1-tetralone | 79580-19-3 | C16H12Cl2O | 详情 | 详情 |
| (II) | 30584 | N-[4-(3,4-dichlorophenyl)-3,4-dihydro-1(2H)-naphthalenylidene]-N-methylamine; N-[4-(3,4-dichlorophenyl)-3,4-dihydro-1(2H)-naphthalenylidene]methanamine | C17H15Cl2N | 详情 | 详情 |