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【结 构 式】 
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【分子编号】62690 【品名】methyl 3-methyl-3-[4-(3-methyl-2-thienyl)phenyl]-2-oxiranecarboxylate 【CA登记号】 |
【 分 子 式 】C16H16O3S 【 分 子 量 】288.36724 【元素组成】C 66.64% H 5.59% O 16.64% S 11.12% |
合成路线1
该中间体在本合成路线中的序号：(XV)Preparation of the racemic arylpropionic acid (IX) has been reported through a number of different procedures. 4-Aminoacetophenone (XI) was diazotized to (XII) employing isoamyl nitrite and either acetic or fluoboric acid. Then, the Gomberg-Bachmann coupling of diazonium salt (XII) with 3-methylthiophene (XIII) furnished 4-(3-methyl-2-thienyl)acetophenone (XIV). Subsequent Darzen's condensation of acetophenone (XIV) with methyl chloroacetate (II) afforded the glycidic ester (XV), which was further hydrolyzed to acid (XVI), and then decarboxylated to aldehyde (XVII). Oxidation of (XVII) to the key carboxylic acid was performed by treatment with potassium permanganate
| 【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 |
|---|---|---|---|---|---|---|
| (II) | 10257 | methyl 2-chloroacetate; methyl chloroacetate | 96-34-4 | C3H5ClO2 | 详情 | 详情 |
| (IX) | 62687 | 2-[4-(3-methyl-2-thienyl)phenyl]propanoic acid | C14H14O2S | 详情 | 详情 | |
| (XI) | 27847 | 1-(4-aminophenyl)-1-ethanone | 99-92-3 | C8H9NO | 详情 | 详情 |
| (XII) | 62688 | 4-acetylbenzenediazonium | C8H7N2O | 详情 | 详情 | |
| (XIII) | 12442 | 3-Methylthiophene | 616-44-4 | C5H6S | 详情 | 详情 |
| (XIV) | 62689 | 1-[4-(3-methyl-2-thienyl)phenyl]-1-ethanone | C13H12OS | 详情 | 详情 | |
| (XV) | 62690 | methyl 3-methyl-3-[4-(3-methyl-2-thienyl)phenyl]-2-oxiranecarboxylate | C16H16O3S | 详情 | 详情 | |
| (XVI) | 62691 | 3-methyl-3-[4-(3-methyl-2-thienyl)phenyl]-2-oxiranecarboxylic acid | C15H14O3S | 详情 | 详情 | |
| (XVII) | 62692 | 2-[4-(3-methyl-2-thienyl)phenyl]propanal | C14H14OS | 详情 | 详情 |
合成路线2
该中间体在本合成路线中的序号：(XV)The glycidic ester (XV), obtained as in Scheme 2, was alternatively rearranged to the alpha-keto ester enol form (XXXV) under acidic conditions. Hydrolysis and decarbonylation of (XXXV) employing NaOMe furnished acid (XI)
| 【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 . |