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【结 构 式】 
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【分子编号】20356 【品名】3-chloro-6-fluoro-2-(trifluoromethyl)benzaldehyde 【CA登记号】 |
【 分 子 式 】C8H3ClF4O 【 分 子 量 】226.5575328 【元素组成】C 42.41% H 1.33% Cl 15.65% F 33.54% O 7.06% |
合成路线1
该中间体在本合成路线中的序号：(I)By cyclocondensation of 3-chloro-6-fluoro-2-(trifluoromethyl)benzaldehyde (I), isopropyl 3-aminocrotonate (II) and methyl 4-fluoroacetylacetate (III) by heating at 110 C. The starting products are prepared as follows: Aldehyde (I) is obtained by reaction of 1-chloro-4-fluoro-3-(trifluoromethyl)benzene (IV) with N-methyl-N-phenylformamide (V) by means of butyllithium in TNF. Aminocrotonate (II) is obtained by reaction of isopropyl acetoacetate (VI) with dry ammonia in methanol. Finally, the acylation of 2,2-dimethyl-1,3-dioxane-4,6-dione (VII) with fluoroacetyl chloride (VIII) by means of pyridine in dichloromethane gives 5-(fluoroacetyl)-2,2-dimethyl-1,3-dioxane-4,6-dione (IX), which is then treated with refluxing methanol to give 4-fluoroacetylacetate (III).
| 【1】 Baxter, A.J.G.; Dixon, J.; Gould, K.J.; McInally, T.; Tinker, A.C. (Celltech Group plc); Pharmaceutically active dihydropyridines. EP 0125803 . |
| 【2】 Baxter, A.J.G.; Dixon, J.; Gould, K.J.; Tinker, A.C. (Celltech Group plc); Dihydropyridine derivs.. EP 0174131; ES 8800154; ES 8801632; JP 1986065867 . |
| 【3】 Prous, J.; Castaner, J.; FPL-62129XX. Drugs Fut 1989, 14, 2, 121. |
| 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) | 20356 | 3-chloro-6-fluoro-2-(trifluoromethyl)benzaldehyde | C8H3ClF4O | 详情 | 详情 | |
| (II) | 13331 | isopropyl (E)-3-amino-2-butenoate | 143093-33-8 | C7H13NO2 | 详情 | 详情 |
| (III) | 20358 | methyl 4-fluoro-3-oxobutanoate | C5H7FO3 | 详情 | 详情 | |
| (IV) | 20359 | 1-chloro-4-fluoro-2-(trifluoromethyl)benzene | C7H3ClF4 | 详情 | 详情 | |
| (V) | 20360 | methyl(phenyl)formamide;N-Methylformanilide;N-Formyl-N-methylaniline;Methylphenylformamide;N-methyl-N-phenylformamide;N-Methyl-N-formylaniline;N-Formyl-N-methylaniline | 93-61-8 | C8H9NO | 详情 | 详情 |
| (VI) | 13332 | isopropyl 3-oxobutanoate; Isopropyl acetoacetate | 542-08-5 | C7H12O3 | 详情 | 详情 |
| (VII) | 14738 | Meldrum's acid; 2,2-dimethyl-1,3-dioxane-4,6-dione；Malonic acid cyclic isopropylidene ester | 2033-24-1 | C6H8O4 | 详情 | 详情 |
| (VIII) | 20363 | 2-fluoroacetyl chloride | 359-06-8 | C2H2ClFO | 详情 | 详情 |
| (IX) | 20364 | 5-(2-fluoroacetyl)-2,2-dimethyl-1,3-dioxane-4,6-dione | C8H9FO5 | 详情 | 详情 |