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【结 构 式】 
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【分子编号】15303 【品名】2-[4-(ethoxycarbonyl)-3-hydroxyphenyl]acetic acid 【CA登记号】 |
【 分 子 式 】C11H12O5 【 分 子 量 】224.21328 【元素组成】C 58.93% H 5.39% O 35.68% |
合成路线1
该中间体在本合成路线中的序号：(IV)1) The condensation of 3-methyl-1-[2-(1-piperidinyl)phenyl)butylamine (I) with 2-[3-ethoxy-4-(ethoxycarbonyl)phenyl]acetic acid (II) by means of triphenylphosphine, triethylamine and CCl4 gives the corresponding amide-ester (III), which is then hydrolyzed with NaOH in ethanol/water to the racemic repaglinide. 2) The condensation of amine (I) with 2-[4-(ethoxycarbonyl)-3-hydroxyphenyl]acetic acid (IV) by means of triphenylphosphine as before yields the corresponding amide-ester (V), which is then submitted to ethoxylation with NaH and ethyl bromide in DMF to afford the racemic amide-ester (III), already obtained.
| 【1】 Graul, A.; Castaner, J.; Repaglinide. Drugs Fut 1996, 21, 7, 694. |
| 【2】 Grell, W. (Dr. Karl Thomae GmbH); New solid forms of 2-ethoxy-4-[N-[1-(2-piperidino-phenyl)-3-methyl-1-butyl] aminocarbonylmethyl]benzoic acid, medicines containing them and process for their preparation. AU 8659139; DE 3522604; EP 0207331; ES 8802145; JP 1987000474 . |
| 【3】 Kwak, J.H.; Jeong, Y.N.; Oh, J.I. (LG Chem Ltd.); Novel quinoline carboxylic acid derivs. having 7-(4-amino-methyl-3-oxime)pyrrolidine substituents and processes for their preparation. CA 2151890; EP 0688772; JP 1996041050; US 5633262; US 5698570; US 5776944 . |
| 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) | 15300 | 3-methyl-1-(2-piperidinophenyl)-1-butanamine; 3-methyl-1-(2-piperidinophenyl)butylamine | C16H26N2 | 详情 | 详情 | |
| (II) | 15301 | 2-[3-ethoxy-4-(ethoxycarbonyl)phenyl]acetic acid | C13H16O5 | 详情 | 详情 | |
| (III) | 15302 | ethyl 2-ethoxy-4-(2-[[3-methyl-1-(2-piperidinophenyl)butyl]amino]-2-oxoethyl)benzoate | C29H40N2O4 | 详情 | 详情 | |
| (IV) | 15303 | 2-[4-(ethoxycarbonyl)-3-hydroxyphenyl]acetic acid | C11H12O5 | 详情 | 详情 | |
| (V) | 15304 | ethyl 2-hydroxy-4-(2-[[3-methyl-1-(2-piperidinophenyl)butyl]amino]-2-oxoethyl)benzoate | C27H36N2O4 | 详情 | 详情 |