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【结 构 式】 
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【药物名称】Femoxetine, NNC-20-4963, FG-4963(HCl) 【化学名称】(+)-(3R,4S)-3-[(4-Methoxyphenoxy)methyl]-1-methyl-4-phenylpiperidine 【CA登记号】59859-58-4 【 分 子 式 】C20H25NO2 【 分 子 量 】311.42775 |
【开发单位】Ferrosan A/S (Originator) 【药理作用】Antidepressants, Mood Disorders, Treatment of, PSYCHOPHARMACOLOGIC DRUGS, 5-HT Reuptake Inhibitors |
合成路线1
The reaction of methyl N-methyl-1,2,5,6-tetrahydropyridine-3-carboxylate (I) with phenylmagnesium bromide (A) gives methyl 1-methyl-4-phenylpiperidine-3-carboxylate (II), which is reduced with LiAlH4 yielding 1-methyl-3-hydroxymethyl-4-phenylpiperidine (III), which, in turn is resolved into its optical isomers. The alcohol (III) is esterified with methanesulfonyl chloride in pyridine affording 3-(methansulfonyloxymethyl)-1-methyl-4-phenylpiperidine (IV), which is finally condensed with p-methoxyphenol (B) by means of sodium methoxide in refluxing methanol.
| 【1】 Christensen, J.A.; Squires, R.F.; 4-Phenylpiperidine compounds. DE 2404113; FR 2215233; GB 1422263; JP 49101385; JP 58174363; US 3912743 . |
| 【2】 Chatterjee, S.S.; Femoxetine. Drugs Fut 1977, 2, 5, 309. |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| (A) | 17616 | bromo(phenyl)magnesium; Phenyl Magnesium Bromide | 100-58-3 | C6H5BrMg | 详情 | 详情 |
| (B) | 32744 | 4-methoxyphenol | 150-76-5 | C7H8O2 | 详情 | 详情 |
| (I) | 38648 | methyl 1-methyl-1,2,5,6-tetrahydro-3-pyridinecarboxylate | C8H13NO2 | 详情 | 详情 | |
| (II) | 40118 | methyl (3R,4S)-1-methyl-4-phenyl-3-piperidinecarboxylate | C14H19NO2 | 详情 | 详情 | |
| (III) | 40119 | [(3R,4S)-1-methyl-4-phenylpiperidinyl]methanol | C13H19NO | 详情 | 详情 | |
| (IV) | 40120 | (3R,4S)-1-methyl-3-([[methyl(dimethylene)-lambda(6)-sulfanyl]oxy]methyl)-4-phenylpiperidine | C16H25NOS | 详情 | 详情 |