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【结 构 式】 
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【分子编号】13391 【品名】(1S,4R,5R,8S)-4,8-Dimethyl-7-oxo-2,3-dioxabicyclo[3.3.1]nonane-4-carbaldehyde 【CA登记号】 |
【 分 子 式 】C10H14O4 【 分 子 量 】198.21876 【元素组成】C 60.59% H 7.12% O 32.29% |
合成路线1
该中间体在本合成路线中的序号：(VI)The oxidation of (5R)-(-)-carvone (I) with 3-chloroperbenzoic acid (3-CPB) in dichloromethane gives 5(R)-acetyl-2-methyl-2-cyclohexen-1-one (II), which is condensed with ethyltriphenylphosphonium bromide (III) by means of butyllithium in THF yielding 2-methyl-5(Z)-(1-methyl-1-propenyl)-2-cyclohexen-1-one (IV). The photochemical oxidation of (IV) in acetonitrile catalyzed by methylene blue affords (1R,4RS,5R,8S)-4,8-dimethyl-4-vinyl-2,3-dioxabicyclo[3.3.1]nonan-7-one (V), which is ozonolyzed with O3 in methanol to the corresponding aldehyde as a mixture of enantiomers, which is submitted to crystallization giving the (1S,4R,5R,8S)-isomer (VI). Finally, this compound is submitted to a Wittig condensation with 2,4-bis(trifluoromethyl)benzyltriphenylphosphonium bromide (VII) by means of sodium bis(trimethylsilyl)amide (NaBTSA) in dichloromethane.
| 【1】 Rabasseda, X.; Mealy, N.; Castaner, J.; Arteflene. Drugs Fut 1995, 20, 4, 341. |
| 【2】 Hofheinz, W.; Schmid, G.; Stohler, H. (F. Hoffmann-La Roche AG); Bicyclic peroxide. AU 8823596; EP 0311955; JP 1989132578; US 4977184 . |
| 【3】 Hofheinz, W.; Burgin, H.; Gocke, H.; Jaquet, C.; Masciadri, R.; Schmid, G.; Stohler, H.; Urwyler, H.; Ro 42-1611 (arteflene), a neweffective antimalarial: Chemical structure and biological activity. Trop Med Parasitol 1994, 45, 3, 261-5. |
| 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) | 13386 | (5R)-5-Isopropenyl-2-methyl-2-cyclohexen-1-one; L-(-)-Carvone | 6485-40-1 | C10H14O | 详情 | 详情 |
| (II) | 13387 | (5R)-5-Acetyl-2-methyl-2-cyclohexen-1-one | C9H12O2 | 详情 | 详情 | |
| (III) | 11717 | Ethyl(triphenyl)phosphonium bromide; (Ethyl)triphenylphosphonium bromide | 1530-32-1 | C20H20BrP | 详情 | 详情 |
| (IV) | 13389 | (5R)-2-Methyl-5-[(Z)-1-methyl-1-propenyl]-2-cyclohexen-1-one | C11H16O | 详情 | 详情 | |
| (V) | 13390 | (1S,5R,8S)-4,8-Dimethyl-4-vinyl-2,3-dioxabicyclo[3.3.1]nonan-7-one | C11H16O3 | 详情 | 详情 | |
| (VI) | 13391 | (1S,4R,5R,8S)-4,8-Dimethyl-7-oxo-2,3-dioxabicyclo[3.3.1]nonane-4-carbaldehyde | C10H14O4 | 详情 | 详情 | |
| (VII) | 13392 | [3,5-Bis(trifluoromethyl)benzyl](triphenyl)phosphonium bromide | C27H20BrF6P | 详情 | 详情 |