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【结 构 式】 
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【分子编号】62685 【品名】2-(4-iodophenyl)propanal 【CA登记号】 |
【 分 子 式 】C9H9IO 【 分 子 量 】260.07433 【元素组成】C 41.56% H 3.49% I 48.8% O 6.15% |
合成路线1
该中间体在本合成路线中的序号：(V)The Darzen's condensation of 4-iodoacetophenone (I) with methyl chloroacetate (II) in the presence of NaOMe afforded the glycidic ester (III), which was further hydrolyzed to the corresponding glycidic acid (IV) with NaOH in aqueous ethanol. Subsequent decarboxylation of (IV) under acidic conditions furnished 2-(4-iodophenyl)propionaldehyde (V). After oxidation of aldehyde (V) with sodium chlorite, the resultant carboxylic acid was converted to the corresponding zinc salt (VI) upon treatment with ZnCl2 and NaOH. Coupling of aryl iodide (VI) with the Grignard reagent (VIII) (prepared from 2-bromo-3-methylthiophene (VII)) in the presence of PdCl2 gave rise to the racemic biarylpropionic acid (IX)). The title (R)-enantiomer was then resolved via formation of the diastereoisomeric salts with D-phenylglycine methyl ester (X)
| 【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 |
|---|---|---|---|---|---|---|
| (I) | 51497 | 4'-Iodoacetophenone; 4-Iodoacetophenone; 1-(4-Iodophenyl)ethanone | 13329-40-3 | C8H7IO | 详情 | 详情 |
| (II) | 10257 | methyl 2-chloroacetate; methyl chloroacetate | 96-34-4 | C3H5ClO2 | 详情 | 详情 |
| (III) | 62683 | methyl 3-(4-iodophenyl)-3-methyl-2-oxiranecarboxylate | C11H11IO3 | 详情 | 详情 | |
| (IV) | 62684 | 3-(4-iodophenyl)-3-methyl-2-oxiranecarboxylic acid | C10H9IO3 | 详情 | 详情 | |
| (V) | 62685 | 2-(4-iodophenyl)propanal | C9H9IO | 详情 | 详情 | |
| (VI) | 62686 | C18H16I2O4Zn | 详情 | 详情 | ||
| (VII) | 12443 | 2-Bromo-3-methylthiophene | 14282-76-9 | C5H5BrS | 详情 | 详情 |
| (VIII) | 36973 | bromo(3-methyl-2-thienyl)magnesium | C5H5BrMgS | 详情 | 详情 | |
| (IX) | 62687 | 2-[4-(3-methyl-2-thienyl)phenyl]propanoic acid | C14H14O2S | 详情 | 详情 | |
| (X) | 10717 | methyl (2S)-2-amino-2-phenylethanoate | C9H11NO2 | 详情 | 详情 |
合成路线2
该中间体在本合成路线中的序号：(V)2-(4-Iodophenyl)-2-methyloxirane (XLV) was obtained by addition of dimethylsulfonium methylide to 4-iodoacetophenone (I). Rearrangement of epoxide (XLV) in the presence of molecular sieves led to aldehyde (V), which was protected as the dimethyl acetal (XLVI) upon treatment with trimethyl orthoformate. Palladium-catalyzed condensation of the Grignard reagent (VIII) with aryl iodide (XLVI) furnished the biaryl adduct (XLVII). This was subsequently hydrolyzed to the key aldehyde (XVII) employing AcOH
| 【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 |
|---|---|---|---|---|---|---|
| (I) | 51497 | 4'-Iodoacetophenone; 4-Iodoacetophenone; 1-(4-Iodophenyl)ethanone | 13329-40-3 | C8H7IO | 详情 | 详情 |
| (V) | 62685 | 2-(4-iodophenyl)propanal | C9H9IO | 详情 | 详情 | |
| (VIII) | 36973 | bromo(3-methyl-2-thienyl)magnesium | C5H5BrMgS | 详情 | 详情 | |
| (XVII) | 62692 | 2-[4-(3-methyl-2-thienyl)phenyl]propanal | C14H14OS | 详情 | 详情 | |
| (XLV) | 62715 | 2-(4-iodophenyl)-2-methyloxirane | C9H9IO | 详情 | 详情 | |
| (XLVI) | 62716 | 1-(2,2-dimethoxy-1-methylethyl)-4-iodobenzene; 2-(4-iodophenyl)-1-methoxypropyl methyl ether | C11H15IO2 | 详情 | 详情 | |
| (XLVII) | 62717 | 1-methoxy-2-[4-(3-methyl-2-thienyl)phenyl]propyl methyl ether; 2-[4-(2,2-dimethoxy-1-methylethyl)phenyl]-3-methylthiophene | C16H20O2S | 详情 | 详情 |
合成路线3
该中间体在本合成路线中的序号：(V)In an asymmetric synthesis of the title compound, aldehyde (V) was oxidized with sodium chlorite to afford the corresponding racemic acid, which was resolved via formation of the diastereoisomeric salts with cinchonidine. The target (R)-2-(4-iodophenyl)propionic acid (LIV) was then converted to the zinc salt and subsequently coupled to 3-methyl-2-thienylmagnesium bromide (VIII) in the presence of palladium catalyst to provide the desired chiral arylpropionic acid
| 【1】 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 . |