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【结 构 式】

【药物名称】Benoxaprofen, Oraflex

【化学名称】2-[2-(4-Chlorophenyl)benzoxazol-5-yl]propionic acid

【CA登记号】51234-28-7

【 分 子 式 】C16H12ClNO3

【 分 子 量 】301.73194

【开发单位】Lilly (Originator)

【药理作用】ANALGESIC AND ANESTHETIC DRUGS, Analgesic Drugs, Non-Opioid Analgesics

合成路线1

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
Extended Information