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【结 构 式】 
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【分子编号】37090 【品名】4-fluorobenzamide 【CA登记号】824-75-9 |
【 分 子 式 】C7H6FNO 【 分 子 量 】139.1291832 【元素组成】C 60.43% H 4.35% F 13.66% N 10.07% O 11.5% |
合成路线1
该中间体在本合成路线中的序号：(I)The reaction of p-fluorobenzamide (I) with phosphorus pentachloride (II) in refluxing CCl4, followed by a treatment with formic acid gives N-(dichlorophosphinyl)-p-fluorobenzamide (III), which is then treated with NH3 in CHCl3.
| 【1】 Blancafort, P.; Castaner, J.; Serradell, M.N.; Flurofamide. Drugs Fut 1982, 7, 10, 734. |
| 【2】 Bayless, A.V.; Millner, O.E. Jr. (Norwich Eaton); N-[Diaminophosphinyl]arylcarboxamides. US 4182881 . |
合成路线2
该中间体在本合成路线中的序号：(VII)The cyclization of 4-hydroxyacetophenone (I) with 3-chloro-3-methyl-1-butyne (II) gives 5-acetyl-2,2-dimethyl-2H-1-benzopyran (III), which is enantioselectively epoxidized catalyzed by chiral salen Mn(III) catalysts to yield the (3R,4R)-epoxide (IV). The reaction of (IV) with ammonia in ethanol affords the (3R,4S)-aminoalcohol (V), which is finally acylated with 4-fluorobenzoyl chloride (VI) and TEA in dichloromethane to provide the target amide. Alternatively, the target amide can also be obtained by direct cleavage of the epoxide ring of (IV) with 4-fluorobenzamide (VII) by means of tBu-OK in tert-butanol.
| 【1】 Chan, W.N.; et al.; Synthesis of novel trans-4-(substituted-benzamido)-3, 4-dihydro-2H-benzo[b]-pyran-3-ol derivatives as potential anticonvulsant agents with a distinctive binding profile. J Med Chem 1996, 39, 23, 4537. |
| 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) | 18123 | 1-(4-hydroxyphenyl)-1-ethanone; 4'-Hydroxyacetophenone | 99-93-4 | C8H8O2 | 详情 | 详情 |
| (II) | 22416 | 3-chloro-3-methyl-1-butyne | 1111-97-3 | C5H7Cl | 详情 | 详情 |
| (III) | 28706 | 1-(2,2-dimethyl-2H-chromen-6-yl)-1-ethanone | C13H14O2 | 详情 | 详情 | |
| (IV) | 28707 | 1-[(1aR,7bR)-2,2-dimethyl-1a,7b-dihydro-2H-oxireno[2,3-c]chromen-6-yl]-1-ethanone | C13H14O3 | 详情 | 详情 | |
| (V) | 28708 | 1-[(3R,4S)-4-amino-3-hydroxy-2,2-dimethyl-3,4-dihydro-2H-chromen-6-yl]-1-ethanone | C13H17NO3 | 详情 | 详情 | |
| (VI) | 17263 | 4-fluorobenzoyl chloride | 403-43-0 | C7H4ClFO | 详情 | 详情 |
| (VII) | 37090 | 4-fluorobenzamide | 824-75-9 | C7H6FNO | 详情 | 详情 |