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【结 构 式】

【分子编号】47151

【品名】ethyl 4-[[4-(benzyloxy)-2-hydroxy-3,6-dimethylbenzoyl]oxy]-2-hydroxy-3,6-dimethylbenzoate

【CA登记号】

【 分 子 式 】C27H28O7

【 分 子 量 】464.51512

【元素组成】C 69.81% H 6.08% O 24.11%

与该中间体有关的原料药合成路线共 2 条

合成路线1

该中间体在本合成路线中的序号:(X)

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2

该中间体在本合成路线中的序号:(V)

Ethyl ester (II) is alkylated with benzyl chloride (I) by means of K2CO3 in acetone to yield 4-benzyloxy derivative (III), which is then hydrolyzed with KOH in H2O/DMSO to provide carboxylic acid (IV). Depside formation between derivative (IV) and ethyl ester (II) by means of trifluoroacetic anhydride in toluene furnishes ethyl benzoate derivative (V), which is finally hydrogenated over Pd/C in AcOEt to yield the target product.

1 Kumar, S.; Muller, K.; Depsides as non-redox inhibitors of leukotriene B4 biosynthesis and HaCaT cell growth. 1.Novel analogues of barbatic and diffractaic acid. Eur J Med Chem 1999, 34, 12, 1035.
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) 19171 1-(Chloromethyl)benzene; Benzyl chloride 100-44-7 C7H7Cl 详情 详情
(II) 47148 ethyl 2,4-dihydroxy-3,6-dimethylbenzoate C11H14O4 详情 详情
(III) 47149 ethyl 4-(benzyloxy)-2-hydroxy-3,6-dimethylbenzoate C18H20O4 详情 详情
(IV) 47150 4-(benzyloxy)-2-hydroxy-3,6-dimethylbenzoic acid C16H16O4 详情 详情
(V) 47151 ethyl 4-[[4-(benzyloxy)-2-hydroxy-3,6-dimethylbenzoyl]oxy]-2-hydroxy-3,6-dimethylbenzoate C27H28O7 详情 详情
Extended Information