• English
  • 简体中文
Login Register
Current Location: Home > Feedback Help Print

【结 构 式】

【分子编号】57138

【品名】(5S)-5-{[tert-butyl(dimethyl)silyl]oxy}-2-cyclohexen-1-one

【CA登记号】

【 分 子 式 】C12H22O2Si

【 分 子 量 】226.39098

【元素组成】C 63.67% H 9.79% O 14.13% Si 12.41%

与该中间体有关的原料药合成路线共 3 条

合成路线1

该中间体在本合成路线中的序号:(I)

The reaction of the chiral cyclohexenone (I) with H2O2 and NaOH in methanol gives the epoxide (II), which is submitted to a Wittig olefination with the phosphonium bromide (III) and KHMDS in toluene to yield the bromomethylene derivative (IV). The opening of the epoxide ring by means of DIBAL in hexane affords the cyclohexanol (V), which is silylated with Tbdms-Cl and imidazole to provide the bis silyl ether (VI). The reaction of (VI), triisopropyl borate and pinacol by means of t-BuLi in ethyl ether gives the boronic ester (VII), which is condensed with alkyl bromide intermediate (VIII) and catalyzed by PdCl2(dppf) and KOH in THF/water to yield the silylated precursor (IX). Finally, this compound is desilylated by means of aq. HF in THF to provide the target 1-alpha,25-dihydroxy-19-nor-vitamin D3. Alternatively, the intermediate (VIII) is reacted with triisiopropyl borate and pinacol, as before, to give the boronic ester (X), which is condensed with the cyclohexylidenemethyl bromide (VI) and catalyzed by PdCl2(dppf) and KOH in THF/water to yield the already reported silylated precursor (IX).

1 Hanazawa, T.; et al.; Novel synthetic approach to 19-nor-1alpha,25-dihydroxyvitamin D3 and its derivatives by Suzuki-Miyaura coupling in solution and on solid support. Org Lett 2001, 3, 24, 3975.
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) 57138 (5S)-5-{[tert-butyl(dimethyl)silyl]oxy}-2-cyclohexen-1-one C12H22O2Si 详情 详情
(II) 57139 (1S,4S,6S)-4-{[tert-butyl(dimethyl)silyl]oxy}-7-oxabicyclo[4.1.0]heptan-2-one C12H22O3Si 详情 详情
(III) 57140 (bromomethyl)(trimethyl)phosphonium bromide C4H11Br2P 详情 详情
(IV) 57141 ({(1S,3R,6R)-5-[(E)-bromomethylidene]-7-oxabicyclo[4.1.0]hept-3-yl}oxy)(tert-butyl)dimethylsilane; (1S,3R,6R)-5-[(E)-bromomethylidene]-7-oxabicyclo[4.1.0]hept-3-yl tert-butyl(dimethyl)silyl ether C13H23BrO2Si 详情 详情
(V) 57142 (1R,5R)-3-[(Z)-bromomethylidene]-5-{[tert-butyl(dimethyl)silyl]oxy}cyclohexanol C13H25BrO2Si 详情 详情
(VI) 57143 (1R,5R)-3-(bromomethylene)-5-{[tert-butyl(dimethyl)silyl]oxy}cyclohexyl tert-butyl(dimethyl)silyl ether; [((1R,5R)-3-(bromomethylene)-5-{[tert-butyl(dimethyl)silyl]oxy}cyclohexyl)oxy](tert-butyl)dimethylsilane C19H39BrO2Si2 详情 详情
(VII) 57144 tert-butyl(dimethyl)silyl (1R,3R)-3-{[tert-butyl(dimethyl)silyl]oxy}-5-[(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)methylene]cyclohexyl ether; tert-butyl({(1R,3R)-3-{[tert-butyl(dimethyl)silyl]oxy}-5-[(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)methylene]cyclohexyl}oxy)dimethylsilane C25H51BO4Si2 详情 详情
(VIII) 57145 (5R)-5-{(1R,7aR)-4-[(E)-bromomethylidene]-7a-methyloctahydro-1H-inden-1-yl}-1,1-dimethylhexyl trimethylsilyl ether; [((5R)-5-{(1R,7aR)-4-[(E)-bromomethylidene]-7a-methyloctahydro-1H-inden-1-yl}-1,1-dimethylhexyl)oxy](trimethyl)silane C22H41BrOSi 详情 详情
(IX) 57147 [((1R,5R)-3-[2-((1R,7aR)-1-{(1R)-1,5-dimethyl-5-[(trimethylsilyl)oxy]hexyl}-7a-methyloctahydro-4H-inden-4-ylidene)ethylidene]-5-{[tert-butyl(dimethyl)silyl]oxy}cyclohexyl)oxy](tert-butyl)dimethylsilane; (5R)-5-{(1R,7aR)-4-[(E)-2-((3R,5R)-3,5-bis{[tert-butyl(dimethyl)silyl]oxy}cyclohexylidene)ethylidene]-7a-methyloctahydro-4H-inden-1-yl}-1,1-dimethylhexyl trimethylsilyl ether C41H80O3Si3 详情 详情
(X) 57146 (5R)-5-{(1R,7aR)-7a-methyl-4-[(E)-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)methylidene]octahydro-1H-inden-1-yl}-1,1-dimethylhexyl trimethylsilyl ether; [((5R)-5-{(1R,7aR)-7a-methyl-4-[(E)-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)methylidene]octahydro-1H-inden-1-yl}-1,1-dimethylhexyl)oxy](trimethyl)silane C28H53BO3Si 详情 详情

合成路线2

该中间体在本合成路线中的序号:(I)

The epoxidation of the chiral cyclohexenone (I) with H2O2 and NaOH in methanol gives the epoxide (II), which is condensed with triethyl phosphonoacetate (III) by means of NaH in THF to yield the cyclohexylidene acetate (IV). The regioselective opening of the epoxide ring of (V) by means of formic acid, Pd2(dba)3 and Bu3P in chloroform affords the cyclohexanol derivative (V), which is silylated by means of Tbdms-Cl and imidazole to provide the fully silylated compound (VI). The reduction of the ester group of (VI) by means of DIBAL in toluene gives the primary alcohol (VII) (1), which is treated with NCS and Me2S in dichloromethane to yield the chloride compound (VIII). The reaction of (VIII) with lithium diphenylphosphide, followed by oxidation with H2O2 affords the phosphine oxide (IX), which is condensed with the known synthon (X) by means of BuLi in THF to provide the silylated precursor (XI). Finally, this compound is desilylated by means of TBAF in THF to afford the target 1-alpha,25-dihydroxy-19-nor-vitamin D3.

1 Hanazawa, T.; et al.; Efficient and practical synthesis of the A-ring precursor of 19-nor-1alpha,25-dihydroxyvitamin D3 and its (3C- or 2H-labeled derivative. Org Lett 2001, 3, 14, 2205.
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) 57138 (5S)-5-{[tert-butyl(dimethyl)silyl]oxy}-2-cyclohexen-1-one C12H22O2Si 详情 详情
(II) 57139 (1S,4S,6S)-4-{[tert-butyl(dimethyl)silyl]oxy}-7-oxabicyclo[4.1.0]heptan-2-one C12H22O3Si 详情 详情
(III) 10019 Ethyl 2-(diethoxyphosphoryl)acetate; Triethyl phosphonoacetate 867-13-0 C8H17O5P 详情 详情
(IV) 57148 ethyl 2-((1R,4R,6S)-4-{[tert-butyl(dimethyl)silyl]oxy}-7-oxabicyclo[4.1.0]hept-2-ylidene)acetate C16H28O4Si 详情 详情
(V) 57149 ethyl 2-((3R,5R)-3-{[tert-butyl(dimethyl)silyl]oxy}-5-hydroxycyclohexylidene)acetate C16H30O4Si 详情 详情
(VI) 49047 ethyl 2-((3R,5R)-3,5-bis[[tert-butyl(dimethyl)silyl]oxy]cyclohexylidene)acetate C22H44O4Si2 详情 详情
(VII) 49048 2-((3R,5R)-3,5-bis[[tert-butyl(dimethyl)silyl]oxy]cyclohexylidene)-1-ethanol C20H42O3Si2 详情 详情
(VIII) 57150 tert-butyl(dimethyl)silyl (1R,3R)-3-{[tert-butyl(dimethyl)silyl]oxy}-5-(2-chloroethylidene)cyclohexyl ether; tert-butyl{[(1R,3R)-3-{[tert-butyl(dimethyl)silyl]oxy}-5-(2-chloroethylidene)cyclohexyl]oxy}dimethylsilane C20H41ClO2Si2 详情 详情
(IX) 30302 [2-((3R,5R)-3,5-bis[[tert-butyl(dimethyl)silyl]oxy]cyclohexylidene)ethyl](oxo)diphenylphosphorane; 2-((3R,5R)-3,5-bis[[tert-butyl(dimethyl)silyl]oxy]cyclohexylidene)ethyl(diphenyl)phosphine oxide C32H51O3PSi2 详情 详情
(X) 47151 ethyl 4-[[4-(benzyloxy)-2-hydroxy-3,6-dimethylbenzoyl]oxy]-2-hydroxy-3,6-dimethylbenzoate C27H28O7 详情 详情
(XI) 57147 [((1R,5R)-3-[2-((1R,7aR)-1-{(1R)-1,5-dimethyl-5-[(trimethylsilyl)oxy]hexyl}-7a-methyloctahydro-4H-inden-4-ylidene)ethylidene]-5-{[tert-butyl(dimethyl)silyl]oxy}cyclohexyl)oxy](tert-butyl)dimethylsilane; (5R)-5-{(1R,7aR)-4-[(E)-2-((3R,5R)-3,5-bis{[tert-butyl(dimethyl)silyl]oxy}cyclohexylidene)ethylidene]-7a-methyloctahydro-4H-inden-1-yl}-1,1-dimethylhexyl trimethylsilyl ether C41H80O3Si3 详情 详情

合成路线3

该中间体在本合成路线中的序号:(VII)

The reaction of cis,cis-cyclohexane-1,3,5-triol (I) with Ac2O and pyridine gives the triacetate (II), which is monodeacylated by means of porcine liver esterase at pH 7 to yield the diacetate (III). The silylation of the OH group of (III) with Tbdms-Cl , TEA and DMAP in dichloromethane affords the silyl ether (IV), which is submitted to desymmetrization by enzymatic hydrolysis with porcine liver esterase to provide the chiral cyclohexanol derivative (V). The oxidation of (V) by means of PCC in dichloromethane gives the chiral cyclohexanone (VI), which is finally treated with DBU in dichloromethane to yield the intermediate 5(S)-(Tbdms-O)-2-cyclohexenone (VII).

1 Kalkote, U.R.; et al.; Simple, efficient chemoenzymatic synthesis of (S)-5-(tert-butyldimethylsilyloxy)-2-cyclohexenone and enantiomeric ketone intermediates of 19-Nor-1alpha,25-dihydroxyvitamin D3. J Org Chem 2001, 66, 24, 8277.
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) 11800 1,3,5-Cyclohexanetriol; cis,cis-1,3,5-Cyclohexanetriol dihydrate 50409-12-6 C6H12O3 详情 详情
(II) 49040 3,5-bis(acetoxy)cyclohexyl acetate C12H18O6 详情 详情
(III) 57152 (1R,3S)-3-(acetyloxy)-5-hydroxycyclohexyl acetate C10H16O5 详情 详情
(IV) 57153 (1R,3S)-3-(acetyloxy)-5-{[tert-butyl(dimethyl)silyl]oxy}cyclohexyl acetate C16H30O5Si 详情 详情
(V) 57154 (1S,3R,5R)-3-{[tert-butyl(dimethyl)silyl]oxy}-5-hydroxycyclohexyl acetate C14H28O4Si 详情 详情
(VI) 57155 (1R,3S)-3-{[tert-butyl(dimethyl)silyl]oxy}-5-oxocyclohexyl acetate C14H26O4Si 详情 详情
(VII) 57138 (5S)-5-{[tert-butyl(dimethyl)silyl]oxy}-2-cyclohexen-1-one C12H22O2Si 详情 详情
Extended Information