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【结 构 式】 
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【分子编号】10128 【品名】3,3-Dimethyl-2-butanone; Pinacolin 【CA登记号】75-97-8 |
【 分 子 式 】C6H12O 【 分 子 量 】100.16068 【元素组成】C 71.95% H 12.08% O 15.97% |
合成路线1
该中间体在本合成路线中的序号：(V)The synthesis of [14]-labeled stiripentol has been published: The reaction of 3,4-methylenedioxybromobenzene (I) with 14CO2 by means of butyllithium in ether gives 3,4-methylenedioxybenzoic acid (II), which is reduced with LiAlH4 to the corresponding benzyl alcohol (III). Oxidation of (III) with CrO3-pyridine affords the aldehyde (IV), which is condensed with methyl tert-butyl ketone (V) by means of NaOH in refluxing ethanol to give the labeled pentanone (VI). Finally, this compound is reduced to [14C]-labeled stiripentol with NaBH4 in methanol.
| 【1】 Lepage, F. Veyre, A.; Madelmont, J.C.; Labarre, P.; Maurizis, J.C.; Rapp, M.; Dupuy, J.M.; Labelling by 14C and 3H of 4,4-dimethyl-1-(3,4-methylenedioxyphenyl)-1-pentene-3-ol or stiripentol. J Label Compd Radiopharm 1992, 31, 11, 961. |
| 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) | 10124 | 5-Bromo-1,3-benzodioxole; 4-Bromo-1,2-(methylenedioxy)benzene | 2635-13-4 | C7H5BrO2 | 详情 | 详情 |
| (II) | 10125 | 1,3-Benzodioxole-5-carboxylic acid | 94-53-1 | C8H6O4 | 详情 | 详情 |
| (II) | 44584 | 1,3-benzodioxole-5-carboxylic acid | C8H6O4 | 详情 | 详情 | |
| (III) | 10126 | 1,3-Benzodioxol-5-ylmethanol; Helioalcohol | 495-76-1 | C8H8O3 | 详情 | 详情 |
| (III) | 44585 | 1,3-benzodioxol-5-ylmethanol | C8H8O3 | 详情 | 详情 | |
| (IV) | 10127 | 1,3-Benzodioxole-5-carbaldehyde; Heliotropine | 120-57-0 | C8H6O3 | 详情 | 详情 |
| (IV) | 44586 | 1,3-benzodioxole-5-carbaldehyde | C8H6O3 | 详情 | 详情 | |
| (V) | 10128 | 3,3-Dimethyl-2-butanone; Pinacolin | 75-97-8 | C6H12O | 详情 | 详情 |
| (VI) | 10129 | (E)-1-(1,3-Benzodioxol-5-yl)-4,4-dimethyl-1-penten-3-one | C14H16O3 | 详情 | 详情 | |
| (VI) | 44587 | (E)-1-(1,3-benzodioxol-5-yl)-4,4-dimethyl-1-penten-3-one | C14H16O3 | 详情 | 详情 |
合成路线2
该中间体在本合成路线中的序号：(II)The condensation of 3,4-methylenedioxybenzaldehyde (I) with 3,3-dimethyl-2-butanone (II) by means of NaOH in ethanol-water gives 4,4-dimethyl-1-[(3,4-methylenedioxy)phenyl]-1-penten-3-one (III), which is reduced with NaBH4 in methanol.
| 【1】 Vallet, F.M.J.; US 3910959 . |
| 【2】 Astoin, J.; et al.; Action of new ethylenic alcohols on the central nervous system. Eur J Med Chem - Chim Ther 1978, 13, 1, 41-47. |
| 【3】 Castaner, J.; Hillier, K.; Stiripentol. Drugs Fut 1980, 5, 8, 413. |
合成路线3
该中间体在本合成路线中的序号：(II)Alkylation of the lithium enolate of pinacolone (II) with alkyl iodide (I) affords ketone (III). After desilylation of (III) by means of tetrabutylammonium fluoride, the resultant alcohol (IV) is oxidized to the corresponding ketone (V) employing N-methylmorpholine-N-oxide in the presence of a catalytic amount of tetrapropylammonium perruthenate. Wadsworth-Emmons condensation of ketone (V) with the racemic phosphine oxide (VI) provides a diastereomeric mixture of diene adducts (VII). After conversion of (VII) to the corresponding oxime, the desired isomer (VIII) is isolated by column chromatography. Finally, desilylation of (VIII) by means of tetrabutylammonium fluoride provides the title compound.
| 【1】 Posner, G.H.; Kensler, T.W.; Dolan, P.; Peleg, S.; Halford, B.A.; Conceptually new low-calcemic oxime analogues of the hormone 1alpha,25-dihydroxyvitamin D3: Synthesis and biological testing. J Med Chem 2002, 45, 8, 1723. |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| (VIIa) | 57668 | (7R)-7-{(3aS,7aS)-7-[(E)-2-((3S,5R)-3,5-bis{[tert-butyl(dimethyl)silyl]oxy}-2-methylenecyclohexylidene)ethylidene]-3a-methyl-3a,4,5,6,7,7a-hexahydro-1H-inden-3-yl}-2,2-dimethyl-3-octanone | C41H72O3Si2 | 详情 | 详情 | |
| (VIIb) | 57669 | (7R)-7-{(3aS,7aS)-7-[(E)-2-((3R,5S)-3,5-bis{[tert-butyl(dimethyl)silyl]oxy}-2-methylenecyclohexylidene)ethylidene]-3a-methyl-3a,4,5,6,7,7a-hexahydro-1H-inden-3-yl}-2,2-dimethyl-3-octanone | C41H72O3Si2 | 详情 | 详情 | |
| (I) | 42570 | ([(3aS,7S,7aR)-3-[(1R)-3-iodo-1-methylpropyl]-3a-methyl-3a,4,5,6,7,7a-hexahydro-1H-inden-7-yl]oxy)(triethyl)silane; (3aS,7S,7aR)-3-[(1R)-3-iodo-1-methylpropyl]-3a-methyl-3a,4,5,6,7,7a-hexahydro-1H-inden-7-yl triethylsilyl ether | C20H37IOSi | 详情 | 详情 | |
| (II) | 10128 | 3,3-Dimethyl-2-butanone; Pinacolin | 75-97-8 | C6H12O | 详情 | 详情 |
| (III) | 57651 | (7R)-7-{(3aS,7S,7aR)-3a-methyl-7-[(triethylsilyl)oxy]-3a,4,5,6,7,7a-hexahydro-1H-inden-3-yl}-2,2-dimethyl-3-octanone | C26H48O2Si | 详情 | 详情 | |
| (IV) | 57666 | (7R)-7-[(3aS,7S,7aR)-7-hydroxy-3a-methyl-3a,4,5,6,7,7a-hexahydro-1H-inden-3-yl]-2,2-dimethyl-3-octanone | C20H34O2 | 详情 | 详情 | |
| (V) | 57667 | (3aR,7aS)-7a-methyl-1-[(1R)-1,6,6-trimethyl-5-oxoheptyl]-3,3a,5,6,7,7a-hexahydro-4H-inden-4-one | C20H32O2 | 详情 | 详情 | |
| (VI) | 42574 | [2-((3S,5R)-3,5-bis[[tert-butyl(dimethyl)silyl]oxy]-2-methylenecyclohexylidene)ethyl](oxo)diphenylphosphorane; 2-((3S,5R)-3,5-bis[[tert-butyl(dimethyl)silyl]oxy]-2-methylenecyclohexylidene)ethyl(diphenyl)phosphine oxide | C33H51O3PSi2 | 详情 | 详情 | |
| (VIII) | 57670 | (7R)-7-{(3aS,7aS)-7-[(E)-2-((3S,5R)-3,5-bis{[tert-butyl(dimethyl)silyl]oxy}-2-methylenecyclohexylidene)ethylidene]-3a-methyl-3a,4,5,6,7,7a-hexahydro-1H-inden-3-yl}-2,2-dimethyl-3-octanone oxime | C41H73NO3Si2 | 详情 | 详情 |
合成路线4
该中间体在本合成路线中的序号：(II)Alkylation of the lithium enolate of pinacolone (II) with alkyl iodide (I) affords ketone (III), which is then condensed with O-methyl hydroxylamine to produce oxime (IV). After desilylation of (IV) by means of tetrabutylammonium fluoride, the resultant alcohol (V) is oxidized to the corresponding ketone (VI), employing N-methylmorpholine-N-oxide in the presence of a catalytic amount of tetrapropylammonium perruthenate. Wadsworth-Emmons condensation of ketone (VI) with the racemic phosphine oxide (VII) provides a diastereomeric mixture of diene adducts (VIII). After desilylation of (VIII) by means of tetrabutylammonium fluoride, the resultant mixture of diol isomers is separated by column chromatography to furnish the title compound.
| 【1】 Posner, G.H.; Kensler, T.W.; Dolan, P.; Peleg, S.; Halford, B.A.; Conceptually new low-calcemic oxime analogues of the hormone 1alpha,25-dihydroxyvitamin D3: Synthesis and biological testing. J Med Chem 2002, 45, 8, 1723. |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| (VIIIa) | 57655 | (7R)-7-{(3aS,7aS)-7-[(E)-2-((3S,5R)-3,5-bis{[tert-butyl(dimethyl)silyl]oxy}-2-methylenecyclohexylidene)ethylidene]-3a-methyl-3a,4,5,6,7,7a-hexahydro-1H-inden-3-yl}-2,2-dimethyl-3-octanone O-methyloxime | C42H75NO3Si2 | 详情 | 详情 | |
| (VIIIb) | 57656 | (7R)-7-{(3aS,7aS)-7-[(E)-2-((3S,5S)-3,5-bis{[tert-butyl(dimethyl)silyl]oxy}-2-methylenecyclohexylidene)ethylidene]-3a-methyl-3a,4,5,6,7,7a-hexahydro-1H-inden-3-yl}-2,2-dimethyl-3-octanone O-methyloxime | C42H75NO3Si2 | 详情 | 详情 | |
| (I) | 42570 | ([(3aS,7S,7aR)-3-[(1R)-3-iodo-1-methylpropyl]-3a-methyl-3a,4,5,6,7,7a-hexahydro-1H-inden-7-yl]oxy)(triethyl)silane; (3aS,7S,7aR)-3-[(1R)-3-iodo-1-methylpropyl]-3a-methyl-3a,4,5,6,7,7a-hexahydro-1H-inden-7-yl triethylsilyl ether | C20H37IOSi | 详情 | 详情 | |
| (II) | 10128 | 3,3-Dimethyl-2-butanone; Pinacolin | 75-97-8 | C6H12O | 详情 | 详情 |
| (III) | 57651 | (7R)-7-{(3aS,7S,7aR)-3a-methyl-7-[(triethylsilyl)oxy]-3a,4,5,6,7,7a-hexahydro-1H-inden-3-yl}-2,2-dimethyl-3-octanone | C26H48O2Si | 详情 | 详情 | |
| (IV) | 57652 | (7R)-7-{(3aS,7S,7aR)-3a-methyl-7-[(triethylsilyl)oxy]-3a,4,5,6,7,7a-hexahydro-1H-inden-3-yl}-2,2-dimethyl-3-octanone O-methyloxime | C27H51NO2Si | 详情 | 详情 | |
| (V) | 57653 | (7R)-7-[(3aS,7S,7aR)-7-hydroxy-3a-methyl-3a,4,5,6,7,7a-hexahydro-1H-inden-3-yl]-2,2-dimethyl-3-octanone O-methyloxime | C21H37NO2 | 详情 | 详情 | |
| (VI) | 57654 | (3aR,7aS)-1-[(1R)-5-(methoxyimino)-1,6,6-trimethylheptyl]-7a-methyl-3,3a,5,6,7,7a-hexahydro-4H-inden-4-one | C21H35NO2 | 详情 | 详情 | |
| (VII) | 42574 | [2-((3S,5R)-3,5-bis[[tert-butyl(dimethyl)silyl]oxy]-2-methylenecyclohexylidene)ethyl](oxo)diphenylphosphorane; 2-((3S,5R)-3,5-bis[[tert-butyl(dimethyl)silyl]oxy]-2-methylenecyclohexylidene)ethyl(diphenyl)phosphine oxide | C33H51O3PSi2 | 详情 | 详情 |