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【结 构 式】

【分子编号】33202

【品名】(5S)-5-methyl-2(5H)-furanone

【CA登记号】

【 分 子 式 】C5H6O2

【 分 子 量 】98.10144

【元素组成】C 61.22% H 6.16% O 32.62%

与该中间体有关的原料药合成路线共 1 条

合成路线1

该中间体在本合成路线中的序号:(XXI)

The tricyclic sulfone intermediate (XVI) has also been obtained as follows: The Diels-Alder condensation between 4,5,6,7-tetrahydroisobenzofuran (XX) and 5(R)-methylfuran-2(5H)-one (XXI) catalyzed by LiClO4 in ethyl ether gives the unsaturated tricyclic epoxyketone (XXII), which is hydrogenated with H2 over Pd/C in ethanol yielding the corresponding saturated epoxylactone (XXIII). Opening of the epoxide ring of (XXIII) by means of lithium hexamethyldisylazane (LiHMDS) in THF affords the hydroxyketone (XXIV), which is isomerized to (XXV) by means of DBU in hot toluene. The hydrogenation of the double bond of (XXV) with H2 over PtO2 in ethanol gives the saturated hydroxylactone (XXVI) with the correct stereochemical configuration. The reduction of the lactone group of (XXVI) with DIBAL, followed by methylation with BF3/Et2O and methanol affords the cyclic hemiketal (XXVII), which is oxidized at the secondary hydroxyl group with Dess-Martin oxidant to give the tricyclic ketone (XXVIII). The reaction of (XXVIII) with methyltriphenylphosphonium iodide and sodium hexamethyldisilazane (NaHMDS) in ethyl ether yields the corresponding methylene derivative (XXIX), which is hydroxylated with BH3/THF and H2O2/NaOH to provide the expected hydroxymethyl derivative (XXX). The reaction of (XXX) with Ms-Cl and triethylamine in dichloromethane gives the mesylate (XXXI), which is condensed with thiophenol and potassium tert-butoxide in DMSO to yield the previously described phenylsulfanyl intermediate (XV), which is finally oxidized with MCPBA as before to the target tricyclic sulfone intermediate (XVI).

1 Takadoi, M.; et al.; A novel total synthesis of (+)-himbacine, a potent antagonist of the muscarinic receptor of M-2 subtype. Tetrahedron Lett 1999, 40, 17, 3399.
中间体序号 中间体编号 品名 CAS号 分子式 供应商 用于合成
(XV) 33192 (1S,3S,3aS,4R,4aS,8aR,9aS)-3-methyl-4-[(phenylsulfanyl)methyl]dodecahydronaphtho[2,3-c]furan-1-yl methyl ether; (1S,3S,3aS,4R,4aS,8aR,9aS)-1-methoxy-3-methyl-4-[(phenylsulfanyl)methyl]dodecahydronaphtho[2,3-c]furan C21H30O2S 详情 详情
(XVI) 33193 [(1S,3S,3aS,4R,4aS,8aR,9aS)-1-methoxy-3-methyldodecahydronaphtho[2,3-c]furan-4-yl]methyl phenyl sulfone; (1S,3S,3aS,4R,4aS,8aR,9aS)-1-methoxy-3-methyl-4-[(phenylsulfonyl)methyl]dodecahydronaphtho[2,3-c]furan C21H30O4S 详情 详情
(XX) 33201 4,5,6,7-tetrahydro-2-benzofuran C8H10O 详情 详情
(XXI) 33202 (5S)-5-methyl-2(5H)-furanone C5H6O2 详情 详情
(XXII) 33203 (1R,8S,9R,12S,13S)-12-methyl-11,14-dioxatetracyclo[6.5.1.0(2,7).0(9,13)]tetradec-2(7)-en-10-one C13H16O3 详情 详情
(XXIII) 33204 (1S,2S,7R,8R,9R,12S,13S)-12-methyl-11,14-dioxatetracyclo[6.5.1.0(2,7).0(9,13)]tetradecan-10-one C13H18O3 详情 详情
(XXIV) 33205 (3S,3aS,4R,4aS,8aS)-4-hydroxy-3-methyl-3a,4,4a,5,6,7,8,8a-octahydronaphtho[2,3-c]furan-1(3H)-one C13H18O3 详情 详情
(XXV) 33206 (3S,3aS,4R,4aS,9aS)-4-hydroxy-3-methyl-3a,4,4a,5,6,7,8,9a-octahydronaphtho[2,3-c]furan-1(3H)-one C13H18O3 详情 详情
(XXVI) 33207 (3S,3aS,4R,4aS,8aR,9aS)-4-hydroxy-3-methyldecahydronaphtho[2,3-c]furan-1(3H)-one C13H20O3 详情 详情
(XXVII) 33208 (1S,3S,3aS,4R,4aS,8aR,9aS)-1-methoxy-3-methyldodecahydronaphtho[2,3-c]furan-4-ol C14H24O3 详情 详情
(XXVIII) 33209 (1S,3S,3aR,4aS,8aR,9aS)-1-methoxy-3-methyldecahydronaphtho[2,3-c]furan-4(1H)-one C14H22O3 详情 详情
(XXIX) 33210 (1S,3S,3aS,4aS,8aR,9aS)-1-methoxy-3-methyl-4-methylenedodecahydronaphtho[2,3-c]furan; (1S,3S,3aS,4aS,8aR,9aS)-3-methyl-4-methylenedodecahydronaphtho[2,3-c]furan-1-yl methyl ether C15H24O2 详情 详情
(XXX) 33211 [(1S,3S,3aR,4R,4aS,8aR,9aS)-1-methoxy-3-methyldodecahydronaphtho[2,3-c]furan-4-yl]methanol C15H26O3 详情 详情
(XXXI) 33212 [(1S,3S,3aR,4R,4aS,8aR,9aS)-1-methoxy-3-methyldodecahydronaphtho[2,3-c]furan-4-yl]methyl methanesulfonate C16H28O5S 详情 详情
Extended Information