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【结 构 式】 
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【分子编号】40159 【品名】2-(4-amino-3-hydroxyphenyl)propanenitrile 【CA登记号】 |
【 分 子 式 】C9H10N2O 【 分 子 量 】162.19128 【元素组成】C 66.65% H 6.21% N 17.27% O 9.86% |
合成路线1
该中间体在本合成路线中的序号：(IV)The Sandmeyer reaction of 4-aminophenyl-alpha-methylacetonitrile (I) with NaNO2, HCl and H2SO4 gives 4-hydroxyphenyl-alpha-methylacetonitrile (II), which is nitrated with nitric acid in acetic acid yielding 4-hydroxy-3-nitrophenyl-alpha-methylacetonitrile (III). The reduction of (III) with SnCl2.2H2O and HCl in ethanol, or with H2 over Pd/C in the same solvent affords 4-hydroxy-3-aminophenyl-alpha-methylacetonitrile (IV), which is hydrolyzed with refluxing concentrated HCl to 4-hydroxy-3-aminophenyl-alpha-methylacetic acid (V). The esterification of (V) with ethanol and HCl affords the corresponding ethyl ester (VI), which is cyclized with p-chlorobenzoyl chloride (VII) in pyridine at 100 C yielding ethyl 2-(4-chlorophenyl)-alpha-methyl-5-benzoxazoleacetate (VIII). Finally, this compound is hydrolyzed with NaOH in ethanol.
| 【1】 Castañer, J.; Blancafort, P.; Benoxaprofen. Drugs Fut 1977, 2, 9, 565. |
| 【2】 Dunwell, D.W.; et al.; 2-Aryl-5-benzoxazolealkanoic acid derivatives with notable antiinflammatory activity. J Med Chem 1975, 18, 1, 53. |
| 【3】 Dunwell, D.W.; et al. (Lilly Industries Ltd.); Benzoxazole derivatives. DE 2324443; ES 414863; FR 2184966; FR 2284592; GB 1435721; JP 49054363; JP 56167645; US 3912748 . |
| 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) | 40156 | 2-(3-aminophenyl)propanenitrile | C9H10N2 | 详情 | 详情 | |
| (II) | 40157 | 2-(3-hydroxyphenyl)propanenitrile | C9H9NO | 详情 | 详情 | |
| (III) | 40158 | 2-(3-hydroxy-4-nitrophenyl)propanenitrile | C9H8N2O3 | 详情 | 详情 | |
| (IV) | 40159 | 2-(4-amino-3-hydroxyphenyl)propanenitrile | C9H10N2O | 详情 | 详情 | |
| (V) | 40160 | 2-(4-amino-3-hydroxyphenyl)propionic acid | C9H11NO3 | 详情 | 详情 | |
| (V) | 40161 | ethyl 2-(4-amino-3-hydroxyphenyl)propanoate | C11H15NO3 | 详情 | 详情 | |
| (VII) | 10295 | p-Chlorobenzoyl chloride; 4-Chlorobenzoyl chloride | 122-01-0 | C7H4Cl2O | 详情 | 详情 |
| (VIII) | 40162 | ethyl 2-[2-(4-chlorophenyl)-1,3-benzoxazol-5-yl]propanoate | C18H16ClNO3 | 详情 | 详情 |