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【结 构 式】 
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【分子编号】31700 【品名】Methyl 2-hydroxy-2-(4-methoxyphenyl)acetate; Methyl 4-methoxymandelate 【CA登记号】 |
【 分 子 式 】C10H12O4 【 分 子 量 】196.20288 【元素组成】C 61.22% H 6.16% O 32.62% |
合成路线1
该中间体在本合成路线中的序号：(IV)The condensation of 2-chloro-3,4-dimethoxyphenylethylamine (I) with 4-methoxystyrene oxide (II) in refluxing THF gives the hydroxy phenylethylamine (III). The yield of this reaction is only 19%. In a better sequence (I) is heated with methyl 4-methoxymandelate (IV) to give the mandelamide (V), which is then reduced without purification by B2H6 in THF to give (III). The latter is cyclized by treatment with trifluoroacetic acid - sulfuric acid yielding 6-chloro-7,8-dimethoxy-1-(4-methoxyphenyl)-2,3,4,5-tetrahydro-(1H)-3-benzazepine (VI). Finally, this compound is demethylated by treatment with BBr3 in methylene chloride and treated with methanesulfonic acid.
| 【1】 Hieble, J.P.; Wilson III, J.W.; Weinstock, J.; The chemistry and pharmacology of 3-benzazepines derivatives. Drugs Fut 1985, 10, 8, 645. |
| 【2】 Weinstock, J.; Method for 6-bromination of 1-phenyl-2,3,4,5-tetrahydro-1H-3-benzazepine compounds. BE 0860774; DD 2751258; DE 133563; FR 2371430; JP 53063335; NL 7712567; US 4160765; ZA 7705910 . |
| 【3】 Kuo, G.Y.; Holden, K.G.; Tobia, A.J.; Hahn, R.A.; Sarau, H.M.; Ladd, D.L.; Ridley, P.T.; Wilson, J.W.; Setler, P.E.; Bush, C.K.; Yim, N.C.F.; Pfieffer, F.R.; Wardell, J.R.; Weinstock, J.; Separation of potent central and renal dopamine agonist activity in substituted 6-chloro-2,3,4,5-tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepines. J Med Chem 1980, 23, 9, 973-975. |
| 【4】 Weinstock, J. (SmithKline Beecham plc); Benz-tetrasubstituted 1-phenyl-2,3,4,5-tetrahydro-1H-3-benzazepines. EP 0004794; JP 54135787; JP 63065663B; US 4171359 . |
| 【5】 Castaner, J.; Serradell, M.N.; Blancafort, P.; SKF-82,526-J. Drugs Fut 1982, 7, 1, 32. |
| 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) | 42037 | 2-chloro-3,4-dimethoxyphenethylamine; 2-(2-chloro-3,4-dimethoxyphenyl)-1-ethanamine | 67287-36-9 | C10H14ClNO2 | 详情 | 详情 |
| (II) | 31703 | Methyl 4-(2-oxiranyl)phenyl ether; 4-Methoxystyrene oxide; 2-(4-Methoxyphenyl)oxirane | C9H10O2 | 详情 | 详情 | |
| (III) | 31702 | 2-[(2-chloro-3,4-dimethoxyphenethyl)amino]-1-(4-methoxyphenyl)-1-ethanol | C19H24ClNO4 | 详情 | 详情 | |
| (IV) | 31700 | Methyl 2-hydroxy-2-(4-methoxyphenyl)acetate; Methyl 4-methoxymandelate | C10H12O4 | 详情 | 详情 | |
| (V) | 31701 | N-(2-chloro-3,4-dimethoxyphenethyl)-2-hydroxy-2-(4-methoxyphenyl)acetamide | C19H22ClNO5 | 详情 | 详情 | |
| (VI) | 31704 | 4-(6-chloro-7,8-dimethoxy-2,3,4,5-tetrahydro-1H-3-benzazepin-1-yl)phenyl methyl ether; 6-chloro-7,8-dimethoxy-1-(4-methoxyphenyl)-2,3,4,5-tetrahydro-1H-3-benzazepine | C19H22ClNO3 | 详情 | 详情 |