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【结 构 式】 
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【分子编号】45712 【品名】(E)-2-chloro-3-hydroxy-2-propenal 【CA登记号】 |
【 分 子 式 】C3H3ClO2 【 分 子 量 】106.50832 【元素组成】C 33.83% H 2.84% Cl 33.29% O 30.04% |
合成路线1
该中间体在本合成路线中的序号：(XXIX)Finally, etoricoxib is obtained by several related ways: Cyclization of ketosulfone (XXIV) with 2-chloromalondialdehyde (XXIX) or the aniline derivative (XXX) and ammonium acetate in hot propionic acid. Cyclization of ketosulfone (XXIV) with aminoacrolein (XXXI) in the absence of ammonium acetate. Aminoacrolein (XXXI) is prepared by treatment of chloromalondialdehyde (XXIX) with isopropanol, yielding the ether (XXXII) and followed by reaction with ammoniun hydroxide. Cyclization of the lithium enolate of ketosulfone (XXIV) with 2,3-dichloroacrolein (XXXIII) -- obtained by treatment of chloromalondialdehyde (XXIX) with oxalyl chloride and DMF in toluene -- followed by reaction with ammonium acetate or anhydrous ammonia. Reaction of ketosulfone (XXIV) with 2-chloro-1,3-bis(dimethylamino)trimethinium hexaflourophosphate salt (XXXIV) in the presence of an equimolar amount of t-BuOK followed by treatment with HOAc/TFA and then heating at reflux with an excess of ammonium hydroxide. 2-Chloro-1,3-bis(dimethylamino)trimethinium hexaflourophosphate salt (XXXIV) is obtained by reaction of chloroacetic acid (XXXV) with hot dimethylformamide (XXXVI) and POCl3, and then the reaction mixture is treated with 5N NaOH and hexafluorophosphoric acid in water.
| 【1】 Davies, I.W.; Marcoux, J.-F.; Wu, J.; et al.; An efficient preparation of vinamidinium hexafluorophosphate salts. J Org Chem 2000, 65, 15, 4571. |
| 【2】 Castañer, R.M.; Silvestre, J.S.; Sorbera, L.A.; Castañer, J.; Etoricoxib. Drugs Fut 2001, 26, 4, 346. |
| 【3】 Davies, I.W.; Marcoux, J.-F.; Corley, E.G.; et al.; A practical synthesis of a COX-2-specific inhibitor. J Org Chem 2000, 65, 25, 8415. |
| 【4】 Rossen, K.; Robbins, M.A.; Corley, E.G.; Wu, J.; Davies, I.W.; Marcoux, J.-F.; Reider, P.J.; Pye, P.; Larsen, R.D.; Annulation of ketones with vinamidinium hexafluorophosphate salts: An efficient preparation of trisubstituted pyridines. Org Lett 2000, 2, 15, 2339. |
| 【5】 Corley, E.G.; Davies, I.W.; Larsen, R.D.; Rossen, K.; Pye, P.J. (Merck & Co., Inc.); Process for synthesizing COX-2 inhibitors. US 6040319; WO 9955830 . |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| (XXIV) | 45711 | 1-(6-methyl-3-pyridinyl)-2-[4-(methylsulfonyl)phenyl]-1-ethanone | C15H15NO3S | 详情 | 详情 | |
| (XXIX) | 45712 | (E)-2-chloro-3-hydroxy-2-propenal | C3H3ClO2 | 详情 | 详情 | |
| (XXX) | 45714 | (E)-3-anilino-2-chloro-2-propenal | C9H8ClNO | 详情 | 详情 | |
| (XXXI) | 45716 | (E)-3-amino-2-chloro-2-propenal | C3H4ClNO | 详情 | 详情 | |
| (XXXII) | 45715 | (E)-2-chloro-3-isopropoxy-2-propenal | C6H9ClO2 | 详情 | 详情 | |
| (XXXIII) | 45713 | (E)-2,3-dichloro-2-propenal | C3H2Cl2O | 详情 | 详情 | |
| (XXXIV) | 45717 | C7H14ClF6N2P | 详情 | 详情 | ||
| (XXXV) | 11847 | 2-Chloroacetic acid; Chloroacetic Acid | 79-11-8 | C2H3ClO2 | 详情 | 详情 |
| (XXXVI) | 33491 | Dimethylformamide | 68-12-2 | C3H7NO | 详情 | 详情 |
| (XXXVII) | 45718 | N-[(E)-2-chloro-3-(dimethylamino)-2-propenylidene]-N-methylmethanaminium chloride | C7H14Cl2N2 | 详情 | 详情 |