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【结 构 式】 
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【分子编号】68028 【品名】1-(4-methoxyphenyl)-2-methylpropan-2-ol 【CA登记号】 |
【 分 子 式 】C11H16O2 【 分 子 量 】180.24684 【元素组成】C 73.3% H 8.95% O 17.75% |
合成路线1
该中间体在本合成路线中的序号：(XX)N-Protection of 4-(2-amino-2-methylpropyl)phenol (XVI) with CbzCl by means of na2Co3 in CH2Cl2/H2o yields the benzyl carbamate (XVII), which is then O-alkylated with MeI using K2Co3 in DMF to give the methyl ether (XVIII). Finally, compound (XVIII) is N-deprotected by means of H2 over Pd/C in MeoH .
In an alternative method, addition of MeMgCl to 1-(4-methoxyphenyl) acetone (XIX) in toluene produces 1-(4-methoxyphenyl)-2-methyl-2-propanol (XX), which then undergoes Ritter reaction with acetonitrile in the presence of H2So4 in AcoH to afford the N-substituted acetamide (XXI) . Finally, amide (XXI) is hydrolyzed with naoH or KoH in ethoxyethanol/ethylene glycol at 150 °C (III) .
| 【1】 Bouyssou, T., Hoenke, C., Rudolf, K. et al. Discovery of olodaterol, a novel inhaled b2-adrenoceptor agonist with a 24 h bronchodilatory efficacy. Bioorg Med Chem Lett 2010, 20(4): 1410-4. |
| 【2】 Krueger, T., Ries, U., Schnaubelt, J., Rall, W., Leuter, Z.A., Duran, A., Soyka, R. (Boehringer Ingelheim Pharma GmbH & Co. KG). Method for producing betamimetics. EP 1917253, JP 2009504708, US 201114859, Wo 2007020227. |
| 【3】 Rodriguez Dehli, J.M., Hagenkoetter, R., Schul, M., Stange, C. (Boehringer Ingelheim Pharma GmbH & Co. KG). Method for producing betamimetics. EP 2125759, JP 2010516739, US 2010022770, Wo 2008090193. |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| (III) | 68014 | 2-(4-methoxyphenyl)-1,1-dimethylethylamine | C11H17NO | 详情 | 详情 | |
| (XVI) | 29476 | 4-(2-amino-2-methylpropyl)phenol | 51706-55-9 | C10H15NO | 详情 | 详情 |
| (XVII) | 68026 | benzyl (1-(4-hydroxyphenyl)-2-methylpropan-2-yl)carbamate | C18H21NO3 | 详情 | 详情 | |
| (XVIII) | 68027 | benzyl (1-(4-methoxyphenyl)-2-methylpropan-2-yl)carbamate | C19H23NO3 | 详情 | 详情 | |
| (XIX) | 10038 | 4-Methoxyphenylacetone; 1-(4-Methoxyphenyl)acetone | 122-84-9 | C10H12O2 | 详情 | 详情 |
| (XX) | 68028 | 1-(4-methoxyphenyl)-2-methylpropan-2-ol | C11H16O2 | 详情 | 详情 | |
| (XXI) | 68029 | N-(1-(4-methoxyphenyl)-2-methylpropan-2-yl)acetamide | C13H19NO2 | 详情 | 详情 |