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【结 构 式】 
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【分子编号】13899 【品名】methyl 5-chloro-2-hydroxy-3-(2-methyl-2-propenyl)benzoate 【CA登记号】 |
【 分 子 式 】C12H13ClO3 【 分 子 量 】240.68612 【元素组成】C 59.88% H 5.44% Cl 14.73% O 19.94% |
合成路线1
该中间体在本合成路线中的序号：(V)1) The esterification of 5-chloro-2-hydroxybenzoic acid (I) with methanol - HCl gives the corresponding methyl ester (II), which is alkylated with 3-chloro-2-methylpropene (III) to afford methyl 5-chloro-2-(2-methyl-2-propenyloxy)benzoate (IV). The rearrangement of (IV) by heating with N-methylpyrrolidine yields methyl 5-chloro-2-hydroxy-3-(2-methyl-2-propenyl)benzoate (V). The cyclization of (V) in formic acid followed by hydrolysis with NaOH gives 5-chloro-2,2-dimethyl-2,3-dihydrobenzofuran-7-carboxylic acid (VI), which is finally treated with SOCl2, condensed with 3alpha-aminotropane (VII) and treated with maleic acid.
| 【1】 Cohen, M.L.; Lacefield, W.B. (Eli Lilly and Company); Improvements in or relating to specific 5-HT3 antagonists. AU 8821916; EP 0307172; JP 1989110684 . |
| 【2】 Robertson, D.W.; Bloomquist, W.; Pfiefer, W.; Cohen, M.L.; Simon, R.L.; Lacefield, W.B.; Zatosetron, a potent, selective, and long-acting 5-HT3 receptor antagonist: Synthesis and structure-activity relationships. J Med Chem 1992, 35, 2, 310-9. |
| 【3】 Graul, A.; Castaner, J.; Prous, J.; Zatosetron Maleate. Drugs Fut 1994, 19, 9, 850. |
| 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) | 13895 | 5-Chloro-2-hydroxybenzoic acid; 5-Chlorosalicylic acid | 321-14-2 | C7H5ClO3 | 详情 | 详情 |
| (II) | 13714 | Methyl 5-chloro-2-hydroxybenzoate; Methyl 5-chlorosalicylate | 4068-78-4 | C8H7ClO3 | 详情 | 详情 |
| (III) | 12127 | 3-Chloro-2-methyl-1-propene; Isobutenyl chloride | 563-47-3 | C4H7Cl | 详情 | 详情 |
| (IV) | 13898 | methyl 5-chloro-2-[(2-methyl-2-propenyl)oxy]benzoate | C12H13ClO3 | 详情 | 详情 | |
| (V) | 13899 | methyl 5-chloro-2-hydroxy-3-(2-methyl-2-propenyl)benzoate | C12H13ClO3 | 详情 | 详情 | |
| (VI) | 13900 | 5-Chloro-2,2-dimethyl-2,3-dihydro-1-benzofuran-7-carboxylic acid | C11H11ClO3 | 详情 | 详情 | |
| (VII) | 12412 | (1R,5S)-8-Methyl-8-azabicyclo[3.2.1]octan-3-amine; (1R,5S)-8-Methyl-8-azabicyclo[3.2.1]oct-3-ylamine | C8H16N2 | 详情 | 详情 |