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【结 构 式】 
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【分子编号】37199 【品名】(4S)-1-[4-(tert-butyl)phenyl]-4-([[methyl(dimethylene)-lambda(6)-sulfanyl]oxy]methyl)-2-pyrrolidinone 【CA登记号】 |
【 分 子 式 】C18H27NO2S 【 分 子 量 】321.48392 【元素组成】C 67.25% H 8.47% N 4.36% O 9.95% S 9.97% |
合成路线1
该中间体在本合成路线中的序号：(IX)The Michael addition of 4-tert-butylaniline (I) with 2-methylenesuccinic acid (II) followed by cyclization gives racemic 1-(4-tert-butylphenyl)-5-oxopyrrolidine-3-carboxylic acid (III) (1), which is treated with SOCl2 and condensed with (S)(-)-1-(4-methylphenyl)ethylamine (IV) to yield a diastereomeric mixture of amides (V). The resolution of (V) by silicagel chromatography affords the (S,S)-diastereomer (VI), which is treated with N2O4 and NaOAc in CCl4 to provide 1-(4-tert-butylphenyl)-5-oxopyrrolidine-3(S)-carboxylic acid (VII). The reduction of (VII) with BH3/THF in dichloromethane gives the corresponding carbinol (VIII), which is treated with MsCl and TEA in dichloromethane to yield the mesylate (IX). The condensation of (IX) with 4-hydroxybenzoic acid methyl ester (X) by means of K2CO3 in DMF affords the corresponding phenyl ether (XI), which is finally hydrolyzed with HCl/AcOH to furnish the target compound.
| 【1】 Ohno, T.; Ogawa, K.; Yano, S.; Kobayashi, K.; Shirasaka, T.; Yamada, H.; Yamamoto, A.; Synthesis of the optical isomers of 4-[1-(4-tert-butylphenyl)-2-oxo-pyrrolidine-4-yl]methyloxybenzoic acid (S-2) and their biological evaluation as antilipidemic agent. Chem Pharm Bull 1999, 47, 11, 1549. |
| 【2】 Watanabe, S.; et al.; Synthesis of 4-[1-(substituted phenyl)-2-oxo-pyrrolidin-4-yl]methyloxybenzoic acids and related compounds, and their inhibitory capacities toward fatty-acid and sterol biosyntheses. Eur J Med Chem 1994, 29, 675. |
| 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) | 27492 | 4-(tert-butyl)aniline | 769-92-6 | C10H15N | 详情 | 详情 |
| (II) | 27493 | 2-methylenesuccinic acid | 97-65-4 | C5H6O4 | 详情 | 详情 |
| (III) | 27494 | 1-[4-(tert-butyl)phenyl]-5-oxo-3-pyrrolidinecarboxylic acid | C15H19NO3 | 详情 | 详情 | |
| (IV) | 37195 | (2S)-2-(4-methylphenyl)-1-propanamine; (2S)-2-(4-methylphenyl)propylamine | C10H15N | 详情 | 详情 | |
| (V) | 37196 | 1-[4-(tert-butyl)phenyl]-N-[(2S)-2-(4-methylphenyl)propyl]-5-oxo-3-pyrrolidinecarboxamide | C25H32N2O2 | 详情 | 详情 | |
| (VI) | 37197 | (3S)-1-[4-(tert-butyl)phenyl]-N-[(2S)-2-(4-methylphenyl)propyl]-5-oxo-3-pyrrolidinecarboxamide | C25H32N2O2 | 详情 | 详情 | |
| (VII) | 37198 | (3S)-1-[4-(tert-butyl)phenyl]-5-oxo-3-pyrrolidinecarboxylic acid | C15H19NO3 | 详情 | 详情 | |
| (VIII) | 27499 | (4S)-1-[4-(tert-butyl)phenyl]-4-(hydroxymethyl)-2-pyrrolidinone | C15H21NO2 | 详情 | 详情 | |
| (IX) | 37199 | (4S)-1-[4-(tert-butyl)phenyl]-4-([[methyl(dimethylene)-lambda(6)-sulfanyl]oxy]methyl)-2-pyrrolidinone | C18H27NO2S | 详情 | 详情 | |
| (X) | 10251 | methyl 4-hydroxybenzoate; Methyl p-hydroxybenzoate | 99-76-3 | C8H8O3 | 详情 | 详情 |
| (XI) | 27501 | methyl 4-([(3S)-1-[4-(tert-butyl)phenyl]-5-oxopyrrolidinyl]methoxy)benzoate | C23H27NO4 | 详情 | 详情 |