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【结 构 式】 
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【药物名称】JTT-608 【化学名称】trans-4-(4-Methylcyclohexyl)-4-oxobutanoic acid 【CA登记号】195137-72-5, 195138-09-1 (cis-isomer), 220203-23-6 (undefined isomer) 【 分 子 式 】C11H18O3 【 分 子 量 】198.26431 |
【开发单位】Japan Tobacco (Originator) 【药理作用】Antidiabetic Drugs, ENDOCRINE DRUGS, Type 2 Diabetes Mellitus, Agents for, Insulin Secretagogues, K(ATP) Channel Blockers |
合成路线1
The reaction of di-tert-butyl malonate (I) with ethyl 2-bromoacetate (II) by means of NaH in THF gives di-tert-butyl 2-(ethoxycarbonylmethyl)malonate (III), which is condensed with trans-4-methylcyclohexylcarbonyl chloride (IV) by means of NaH in THF, and without isolation is treated with p-toluenesulfonic acid in refluxing toluene to afford trans-4-(4-methylcyclohexyl)-4-oxobutyric acid ethyl ester (V). Finally, this compound is hydrolyzed with aqueous NaOH.
| 【1】 Shinkai, H.; Ozeki, H.; Motomura, T.; Ohta, T.; Furukawa, N.; Uchida, I.; 4-(trans-4-Methylcyclohexyl)-4-oxobutyric acid (JTT-608). A new class of antidiabetic agent. J Med Chem 1998, 41, 27, 5420. |
| 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) | 14346 | di(tert-butyl) malonate; Di-tert-butyl malonate | 541-16-2 | C11H20O4 | 详情 | 详情 |
| (II) | 16640 | Ethyl 2-bromoacetate; Ethyl bromoacetate | 105-36-2 | C4H7BrO2 | 详情 | 详情 |
| (III) | 24798 | 1,1-di(tert-butyl) 2-ethyl 1,1,2-ethanetricarboxylate | C15H26O6 | 详情 | 详情 | |
| (IV) | 24799 | 4-methylcyclohexanecarbonyl chloride | C8H13ClO | 详情 | 详情 | |
| (V) | 24800 | ethyl 4-(4-methylcyclohexyl)-4-oxobutanoate | C13H22O3 | 详情 | 详情 |