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【结 构 式】 
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【分子编号】62704 【品名】3-chloro-2-hydroxy-3-[4-(3-methyl-2-thienyl)phenyl]butanenitrile 【CA登记号】 |
【 分 子 式 】C15H14ClNOS 【 分 子 量 】291.801 【元素组成】C 61.74% H 4.84% Cl 12.15% N 4.8% O 5.48% S 10.99% |
合成路线1
该中间体在本合成路线中的序号：(XXXIII)Glycidonitrile (XXXII) was prepared by condensation of ketone (XIV) with chloroacetonitrile (XXXI) under Darzens conditions. Epoxide ring opening in (XXXII) by HCl in toluene provided the chlorohydrin (XXXIII). Acetylation of (XXXIII), followed by dehydrohalogenation led to the acetoxy acrylonitrile (XXXIV). Hydrolysis and decarbonylation of (XXXIV) provided an alternative access to the arylpropionic acid (IX)
| 【2】 Arai, H.; Tanaka, K.; Watanabe, I.; Kodama, T.; Hirano, H.; Abe, N.; Nakabayashi, M. (Toyama Chemical Co., Ltd.); Novel 2-[4-(3-methyl-2-thienyl)phenyl]propionic acid and pharmaceutically acceptable salt thereof and method for treating symptoms of inflammation and pain. US 4230719 . |
| 【1】 Kodama, T.; Nakabayashi, M.; Watanabe, I.; Hirano, Y.; Abe, N.; Tanaka, K.; Arai, H. (Toyama Chemical Co., Ltd.); 2-[4-(3-Methyl-2-thienyl)phenyl]propionic acid derivs. and its non-toxic salts. DE 2850485; JP 1981049376 . |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| (IX) | 62687 | 2-[4-(3-methyl-2-thienyl)phenyl]propanoic acid | C14H14O2S | 详情 | 详情 | |
| (XIV) | 62689 | 1-[4-(3-methyl-2-thienyl)phenyl]-1-ethanone | C13H12OS | 详情 | 详情 | |
| (XXXI) | 14443 | 2-chloroacetonitrile; chloroacetonitrile | 107-14-2 | C2H2ClN | 详情 | 详情 |
| (XXXII) | 62703 | 3-methyl-3-[4-(3-methyl-2-thienyl)phenyl]-2-oxiranecarbonitrile | C15H13NOS | 详情 | 详情 | |
| (XXXIII) | 62704 | 3-chloro-2-hydroxy-3-[4-(3-methyl-2-thienyl)phenyl]butanenitrile | C15H14ClNOS | 详情 | 详情 | |
| (XXXIV) | 62705 | (Z)-1-cyano-2-[4-(3-methyl-2-thienyl)phenyl]-1-propenyl acetate | C17H15NO2S | 详情 | 详情 |
合成路线2
该中间体在本合成路线中的序号：(XXXIII)The chlorohydrin (XXXIII), obtained as in Scheme 8, was converted to enol ether (XXXVI) via O-alkylation with bromoethane and sodium amide, followed by basic dehydrohalogenation. Acid hydrolysis of enol ether (XXXVI) produced the keto nitrile (XXXVII), which was then hydrolyzed and decarbonylated to acid (IX)
| 【2】 Arai, H.; Tanaka, K.; Watanabe, I.; Kodama, T.; Hirano, H.; Abe, N.; Nakabayashi, M. (Toyama Chemical Co., Ltd.); Novel 2-[4-(3-methyl-2-thienyl)phenyl]propionic acid and pharmaceutically acceptable salt thereof and method for treating symptoms of inflammation and pain. US 4230719 . |
| 【1】 Kodama, T.; Nakabayashi, M.; Watanabe, I.; Hirano, Y.; Abe, N.; Tanaka, K.; Arai, H. (Toyama Chemical Co., Ltd.); 2-[4-(3-Methyl-2-thienyl)phenyl]propionic acid derivs. and its non-toxic salts. DE 2850485; JP 1981049376 . |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| (IX) | 62687 | 2-[4-(3-methyl-2-thienyl)phenyl]propanoic acid | C14H14O2S | 详情 | 详情 | |
| (XXXIII) | 62704 | 3-chloro-2-hydroxy-3-[4-(3-methyl-2-thienyl)phenyl]butanenitrile | C15H14ClNOS | 详情 | 详情 | |
| (XXXVI) | 62707 | (Z)-2-ethoxy-3-[4-(3-methyl-2-thienyl)phenyl]-2-butenenitrile | C17H17NOS | 详情 | 详情 | |
| (XXXVII) | 62708 | 3-[4-(3-methyl-2-thienyl)phenyl]-2-oxobutanenitrile | C15H13NOS | 详情 | 详情 |