|
【结 构 式】 
|
【分子编号】56149 【品名】diethyl 2-(2-chlorobenzyl)malonate 【CA登记号】 |
【 分 子 式 】C14H17ClO4 【 分 子 量 】284.73928 【元素组成】C 59.06% H 6.02% Cl 12.45% O 22.48% |
与该中间体有关的原料药合成路线共 1 条
合成路线1
该中间体在本合成路线中的序号：(XV)In an alternative procedure, alkylation of diethyl malonate with 2-chlorobenzyl chloride (XIV) afforded malonate (XV), which underwent hydrolysis and further decarboxylation to the arylpropionic acid (XVI) upon refluxing with HCl and HOAc. Coupling of acid (XVI) with the chiral amine (III) to give amide (XVII) was performed in refluxing toluene with azeotropic removal of water or, alternatively, by using DCC as the coupling reagent. Amide (XVII) was finally reduced to the corresponding amine by means of borane in tetrahydrofuran or with DIBAL in CH2Cl2.
| 【1】 Yamazaki, N.; et al.; Nucleophilic addition of methyllithium to chiral oxime ethers: Asymmetric preparation of 1-(aryl)ethylamines and application to a synthesis of calcimimetics (+)-NPS R-568 and its thio analogue. Tetrahedron Lett 2001, 42, 30, 5029. |
| 【2】 D'Ambra, T.E.; Vanwagenen, B.C.; Duff, S.R.; Nelson, W.A. (NPS Pharmaceuticals, Inc.); Method of making a benzylpropanamine. WO 9602492 . |
| 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) | 56140 | (R)-1-(3-Methoxyphenyl)ethylamine; (R)-3-Methoxy-alpha-methylbenzylamine; (R)-m-Methoxy-alpha-methylbenzylamine | 88196-70-7 | C9H13NO | 详情 | 详情 |
| (XIV) | 10205 | 1-Chloro-2-(chloromethyl)benzene; 2-Chlorobenzyl chloride | 611-19-8 | C7H6Cl2 | 详情 | 详情 |
| (XV) | 56149 | diethyl 2-(2-chlorobenzyl)malonate | C14H17ClO4 | 详情 | 详情 | |
| (XVI) | 56150 | 3-(2-Chlorophenyl)propionic acid | 1643-28-3 | C9H9ClO2 | 详情 | 详情 |
| (XVII) | 56151 | 3-(2-chlorophenyl)-N-[(1R)-1-(3-methoxyphenyl)ethyl]propanamide | C18H20ClNO2 | 详情 | 详情 |
Extended Information