ethyl 4-[[4-(benzyloxy)-2-hydroxy-3,6-dimethylbenzoyl]oxy]-2-hydroxy-3,6-dimethylbenzoate -Drug Synthesis Database

【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 合成路线2

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.

参考文献中间体

合成目标

【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.

参考文献中间体

合成目标

【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