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【结 构 式】 
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【分子编号】53450 【品名】ethyl 2-ethoxy-4-(2-ethoxy-2-oxoethyl)benzoate 【CA登记号】n/a |
【 分 子 式 】C15H20O5 【 分 子 量 】280.3208 【元素组成】C 64.27% H 7.19% O 28.54% |
合成路线1
该中间体在本合成路线中的序号：(VI)The reaction of 2-hydroxy-4-methylbenzoic acid (I) with ethyl bromide (II) and K2CO3 in acetone at 150 C gives 2-ethoxy-4-methylbenzoic acid ethyl ester (III), which is brominated with Br2 and AIBN in CCl4 to yield the bromomethyl derivative (IV). The reaction of (IV) with NaCN and benzyl-tributylammonium chloride affords the cyanomethyl compound (V), which is hydrolyzed with HCl (g) in refluxing ethanol to provide 2-ethoxy-4-(ethoxycarbonylmethyl)benzoic acid ethyl ester (VI). Finally, this compound is selectively hydrolyzed with 2N NaOH in ethanol to furnish the target intermediate, the 2-[3-ethoxy-4-(ethoxycarbonyl)phenyl]acetic acid (VII).
| 【1】 Salman, M.; et al.; An efficient and cost-effective synthesis of 3-ethoxy-4-ethoxycarbonyl-phenylacetic acid: A key acid synthon of repaglinide. Org Process Res Dev 2002, 6, 2, 184. |
| 【2】 Grell, W.; Hurnaus, R.; Griss, G.; Sauter, R.; Rupprecht, E.; Mark, M.; Luger, P.; Nar, H.; Wittneben, H.; Muller, P.; Repaglinide and related hypoglycemic benzoic acid derivatives. J Med Chem 1998, 41, 26, 5219. |
| 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) | 53446 | 2-Hydroxy-4-methylbenzoic acid; 2-Hydroxy-p-toluic Acid; 4-Methylsalicylic acid; m-Cresotinic acid | 50-85-1 | C8H8O3 | 详情 | 详情 |
| (II) | 19502 | Propyl bromide; 1-Bromopropane | 106-94-5 | C3H7Br | 详情 | 详情 |
| (III) | 53447 | ethyl 2-ethoxy-4-methylbenzoate | 88709-17-5 | C12H16O3 | 详情 | 详情 |
| (IV) | 53448 | ethyl 4-(bromomethyl)-2-ethoxybenzoate | n/a | C12H15BrO3 | 详情 | 详情 |
| (V) | 53449 | ethyl 4-(cyanomethyl)-2-ethoxybenzoate | n/a | C13H15NO3 | 详情 | 详情 |
| (VI) | 53450 | ethyl 2-ethoxy-4-(2-ethoxy-2-oxoethyl)benzoate | n/a | C15H20O5 | 详情 | 详情 |
| (VII) | 15301 | 2-[3-ethoxy-4-(ethoxycarbonyl)phenyl]acetic acid | C13H16O5 | 详情 | 详情 |