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【结 构 式】 
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【药物名称】Flunoxaprofen, RV-12424, MK-830, Priaxim 【化学名称】(S)-(±)-2-(4-Fluorophenyl)-alpha-methyl-5-benzoxazoleacetic acid 【CA登记号】66934-18-7 【 分 子 式 】C16H12FNO3 【 分 子 量 】285.27734 |
【开发单位】Ravizza (Originator) 【药理作用】Non-Steroidal Antiinflammatory Drugs |
合成路线1
The acidic hydrolysis of 3-nitro-4-hydroxyphenyl-alpha-methylacetonitrile (I) gives 3-nitro-4-hydroxyphenyl-alpha-methylacetic acid (II), which is converted to 3-amino 4-hydroxyphenyl-alpha-methylacetic acid (III) by catalytic hydrogenation. The condensation of (III) with 4-fluorobenzoyl chloride yields 3-(4-fluoro benzamido)-4-hydroxyphenyl-alpha-methylacetic acid (IV), which is cyclized in acidic medium to give 2-(4-fluorophenyl)-alpha-methyl-5-benzoxazoleacetic acid (V). The racemic (V) was optically resolved by N-methyl-D-glucamine, yielding S-(+)-2-(4-fluorophenyl)-alpha-methyl-5-benzoxazoleacetic acid.
| 【1】 Forgione, A.; Flunoxaprofen. Drugs Fut 1986, 11, 3, 187. |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| (A) | 17263 | 4-fluorobenzoyl chloride | 403-43-0 | C7H4ClFO | 详情 | 详情 |
| (I) | 24054 | 2-(4-hydroxy-3-nitrophenyl)propanenitrile | C9H8N2O3 | 详情 | 详情 | |
| (II) | 24055 | 2-(4-hydroxy-3-nitrophenyl)propionic acid | C9H9NO5 | 详情 | 详情 | |
| (III) | 24056 | 2-(3-amino-4-hydroxyphenyl)propionic acid | C9H11NO3 | 详情 | 详情 | |
| (IV) | 24057 | 2-[3-[(4-fluorobenzoyl)amino]-4-hydroxyphenyl]propionic acid | C16H14FNO4 | 详情 | 详情 | |
| (V) | 24058 | 2-[2-(4-fluorophenyl)-1,3-benzoxazol-5-yl]propionic acid | C16H12FNO3 | 详情 | 详情 |