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【结 构 式】 
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【分子编号】33466 【品名】1-(2',4'-difluoro[1,1'-biphenyl]-4-yl)-1-ethanone 【CA登记号】 |
【 分 子 式 】C14H10F2O 【 分 子 量 】232.2296064 【元素组成】C 72.41% H 4.34% F 16.36% O 6.89% |
合成路线1
该中间体在本合成路线中的序号：(V)Compound can be prepared in two different ways both starting from 2,4-difluoroaniline (I): 1) The diazotation of (I) with isoamyl nitrite (B) and condensation with anisole (A) gives 4-(2,4-difluorophenyl)anisole (II), which is hydrolyzed with HI in refluxing acetic acid yielding 4-(2,4-difluorophenyl)phenol (III). Finally, this compound is carbonated with K2CO3 and CO2 at 175 C and 1300 p.s.i. 2) The diazotation of (I) with isoamyl nitrite (B) and then condensation with benzene by means of powdered Cu gives 2,4-difluorobiphenyl (IV), which is acetylated with acetic anhydride by means of AlCl3 in CH2Cl2 yielding 4-(2,4-difluorophenyl)acetophenone (V). The oxidation of (V) with H2O2 in refluxing CH2Cl2 affords 4-(2,4-difluorophenyl)phenyl acetate (VI), which can be hydrolyzed with NaOH in refluxing water to give the phenol (III).
| 【1】 Ruyle, W.V.; et al. (Merck & Co., Inc.); Phenyl benzoic acid compounds in compositions and methods for treating inflammation. US 3674870 . |
| 【2】 Howard, J.; et al. (Merck & Co., Inc.); Chemical products. DE 2532559; FR 2288729; GB 1496231; GB 1496232; JP 51034135 . |
| 【3】 Houser, R.W.; Jones, H. (Merck & Co., Inc.); Process for preparing 4-(2,4-difluorophenyl)-salicyclic acid. US 4225730 . |
| 【4】 Ruyle, W.V.; et al. (Merck & Co., Inc.); Halo-substituted 5-phenylbenzoic acids and their derivatives. GB 1175212 . |
| 【5】 Arrigoni-Martelli, E.; Castaner, J.; Diflunisal. Drugs Fut 1978, 3, 4, 28. |
| 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) | 23767 | Methoxybenzene; Methyl phenyl ether; Anisole | 100-66-3 | C7H8O | 详情 | 详情 |
| (B) | 32169 | 3-Methyl-1-nitrobutane; Isoamyl nitrite | 543-87-3 | C5H11NO2 | 详情 | 详情 |
| (I) | 19462 | 2,4-difluoroaniline; 2,4-difluorophenylamine；2,4-Difluoro-benzenamine;1-Amino-2,4-difluorobenzene | 367-25-9 | C6H5F2N | 详情 | 详情 |
| (II) | 33464 | 2',4'-difluoro[1,1'-biphenyl]-4-yl methyl ether; 2,4-difluoro-4'-methoxy-1,1'-biphenyl | C13H10F2O | 详情 | 详情 | |
| (III) | 14631 | 2',4'-difluoro[1,1'-biphenyl]-4-ol | C12H8F2O | 详情 | 详情 | |
| (IV) | 33465 | 2,4-difluoro-1,1'-biphenyl | C12H8F2 | 详情 | 详情 | |
| (V) | 33466 | 1-(2',4'-difluoro[1,1'-biphenyl]-4-yl)-1-ethanone | C14H10F2O | 详情 | 详情 | |
| (VI) | 33467 | 2',4'-difluoro[1,1'-biphenyl]-4-yl acetate | C14H10F2O2 | 详情 | 详情 |