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【结 构 式】 
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【分子编号】50831 【品名】L-Alanine; L-2-Aminopropionic acid; (S)-(+)-2-Aminopropionic acid; L-2-Aminopropionic acid; (S)-2-Aminopropionic acid; (S)-(+)-Alanine 【CA登记号】56-41-7 |
【 分 子 式 】C3H7NO2 【 分 子 量 】89.09412 【元素组成】C 40.44% H 7.92% N 15.72% O 35.92% |
合成路线1
该中间体在本合成路线中的序号：(I)Treatment of alanine (I) with phosgene in THF provides N-carboxyanhydride derivative (II), which is then coupled to proline (III) by means of KOH and K2CO3 in THF/H2O or acetonitrile to provide dipeptide (IV). Coupling of (IV) to ethyl 2-oxo-4-phenylbutyrate (V) by means of H2 over Raney-Ni in EtOH (or EtOH/HOAc), followed by the corresponding work-up for isomer separation, yields derivative (VI). (In turn, ketoester (V) can be obtained by treatment of 2-phenylethyl bromide (VII) with Mg turnings in refluxing THF, followed by reaction of the resulting Grignard reagent with diethyl oxalate (VIII) in THF). Finally, the desired product is obtained by saponification of the ethyl ester group of (VI) with NaOH.
| 【1】 Blacklock, T.J.; et al.; Synthesis of semisynthetic dipeptides using N-carboxyanhydrides and chiral induction on Raney nickel. A method practical for large scale. J Org Chem 1988, 53, 4, 836. |
| 【2】 Reider, P.J.; Huffman, M.A.; Leblond, C.; Sun, Y. (Merck & Co., Inc.); Improved stereoselective process for enalapril. WO 0017228 . |
| 【3】 Blacklock, T.J.; Shuman, R.F. (Merck & Co., Inc.); Process for preparing polypeptides. US 4510083 . |
| 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) | 50831 | L-Alanine; L-2-Aminopropionic acid; (S)-(+)-2-Aminopropionic acid; L-2-Aminopropionic acid; (S)-2-Aminopropionic acid; (S)-(+)-Alanine | 56-41-7 | C3H7NO2 | 详情 | 详情 |
| (II) | 50829 | (4S)-4-methyl-1,3-oxazolidine-2,5-dione; S-Alanine-N-carboxylic acid anhydride | 2224-52-4 | C4H5NO3 | 详情 | 详情 |
| (III) | 16731 | L-proline | 147-85-3 | C5H9NO2 | 详情 | 详情 |
| (IV) | 32151 | (2S)-1-[(2S)-2-aminopropanoyl]-2-pyrrolidinecarboxylic acid | 13485-59-1 | C8H14N2O3 | 详情 | 详情 |
| (V) | 50832 | ethyl 2-oxo-4-phenylbutanoate | C12H14O3 | 详情 | 详情 | |
| (VI) | 50830 | (2S)-1-((2S)-2-[[(1S)-1-(ethoxycarbonyl)-3-phenylpropyl]amino]propanoyl)-2-pyrrolidinecarboxylic acid | C20H28N2O5 | 详情 | 详情 | |
| (VII) | 20730 | 1-(2-bromoethyl)benzene；1-Bromo-2-phenylethane;(2-Bromoethyl)benzene;Phenethyl bromide | 103-63-9 | C8H9Br | 详情 | 详情 |
| (VIII) | 17571 | Diethyl oxalate; Ethyl 2-ethoxy-2-oxoacetate | 95-92-1 | C6H10O4 | 详情 | 详情 |