2-[(3R,4R,5R)-3,5-bis{[tert-butyl(diphenyl)silyl]oxy}-4-(3-{[tert-butyl(diphenyl)silyl]oxy}propoxy)-2-methylenecyclohexylidene]-1-ethanol -Drug Synthesis Database

【结构式】

【分子编号】59876

【品名】2-[(3R,4R,5R)-3,5-bis{[tert-butyl(diphenyl)silyl]oxy}-4-(3-{[tert-butyl(diphenyl)silyl]oxy}propoxy)-2-methylenecyclohexylidene]-1-ethanol

【CA登记号】

【分子式】C₆₀H₇₄O₅Si₃

【分子量】959.50106

【元素组成】C 75.11% H 7.77% O 8.34% Si 8.78%

与该中间体有关的原料药合成路线共 3 条

合成路线1 合成路线2 合成路线3

合成路线1

该中间体在本合成路线中的序号：(XXX)

Reduction of the ester function of (XXIV) by means of DIBAL afforded alcohol (XXV), which was further protected as the tetrahydropyranyl ether (XXVI). The free secondary hydroxyl of (XXVI) was then alkylated with allyl bromide (XXVII) and NaH to produce the allyl ether (XXVIII). Selective olefin hydroboration at the allyl ether moiety of (XXVIII), followed by oxidative work-up gave rise to the primary alcohol (XXIX). After silylation of (XXIX), the tetrahydropyranyl ether was hydrolyzed with ethanolic HCl providing the tris-O-silylated compound (XXX)

参考文献中间体

合成目标

【1】 Takahashi, T.; Shiono, M. (Kuraray Co., Ltd.); Cyclohexanetriol derivs.. EP 0503630 .

中间体序号	中间体编号	品名	CAS号	分子式	供应商	用于合成
(XXIV)	59871	ethyl 2-((3R,4R,5R)-3,5-bis{[tert-butyl(diphenyl)silyl]oxy}-4-hydroxy-2-methylenecyclohexylidene)acetate		C₄₃H₅₂O₅Si₂	详情	详情
(XXV)	59872	(1R,2R,6R)-2,6-bis{[tert-butyl(diphenyl)silyl]oxy}-4-[(Z)-2-hydroxyethylidene]-3-methylenecyclohexanol		C₄₁H₅₀O₄Si₂	详情	详情
(XXVI)	59873	(1R,2R,6R)-2,6-bis{[tert-butyl(diphenyl)silyl]oxy}-3-methylene-4-[(Z)-2-(tetrahydro-2H-pyran-2-yloxy)ethylidene]cyclohexanol		C₄₆H₅₈O₅Si₂	详情	详情
(XXVII)	11463	3-Bromo-1-propene; 3-Bromopropene；allyl bromide	106-95-6	C₃H₅Br	详情	详情
(XXVIII)	59874	({(1R,2R,3R)-2-(allyloxy)-3-{[tert-butyl(diphenyl)silyl]oxy}-4-methylene-5-[(Z)-2-(tetrahydro-2H-pyran-2-yloxy)ethylidene]cyclohexyl}oxy)(tert-butyl)diphenylsilane; allyl (1R,2R,6R)-2,6-bis{[tert-butyl(diphenyl)silyl]oxy}-3-methylene-4-[(Z)-2-(tetrahydro-2H-pyran-2-yloxy)ethylidene]cyclohexyl ether		C₄₉H₆₂O₅Si₂	详情	详情
(XXIX)	59875	3-({(1R,2R,6R)-2,6-bis{[tert-butyl(diphenyl)silyl]oxy}-3-methylene-4-[(Z)-2-(tetrahydro-2H-pyran-2-yloxy)ethylidene]cyclohexyl}oxy)-1-propanol		C₄₉H₆₄O₆Si₂	详情	详情
(XXX)	59876	2-[(3R,4R,5R)-3,5-bis{[tert-butyl(diphenyl)silyl]oxy}-4-(3-{[tert-butyl(diphenyl)silyl]oxy}propoxy)-2-methylenecyclohexylidene]-1-ethanol		C₆₀H₇₄O₅Si₃	详情	详情

合成路线2

该中间体在本合成路线中的序号：(XXX)

Allyl alcohol (XXX) was converted to chloride (XXXI) by means of N-chlorosuccinimide and dimethylsulfide. Displacement of the chloride ion of (XXXI) with lithium diphenylphosphide, followed by H2O2 oxidation of the resulting phosphine gave the phosphine oxide (XXXII). This was subjected to a Wittig condensation with the functionalized indanone (XXXIII) to produce the triene adduct (XXXIV). Final desilylation of (XXXIV) to the title compound was effected by treatment with tetrabutylammonium fluoride in THF

参考文献中间体

合成目标

【1】 Takahashi, T.; Shiono, M. (Kuraray Co., Ltd.); Cyclohexanetriol derivs.. EP 0503630 .

中间体序号	中间体编号	品名	分子式	供应商	用于合成
(XXX)	59876	2-[(3R,4R,5R)-3,5-bis{[tert-butyl(diphenyl)silyl]oxy}-4-(3-{[tert-butyl(diphenyl)silyl]oxy}propoxy)-2-methylenecyclohexylidene]-1-ethanol	C₆₀H₇₄O₅Si₃	详情	详情
(XXXI)	59877	tert-butyl({(1R,2R,3R)-3-{[tert-butyl(diphenyl)silyl]oxy}-2-(3-{[tert-butyl(diphenyl)silyl]oxy}propoxy)-5-[(Z)-2-chloroethylidene]-4-methylenecyclohexyl}oxy)diphenylsilane; (1R,2R,6R)-2,6-bis{[tert-butyl(diphenyl)silyl]oxy}-4-[(Z)-2-chloroethylidene]-3-methylenecyclohexyl 3-{[tert-butyl(diphenyl)silyl]oxy}propyl ether	C₆₀H₇₃ClO₄Si₃	详情	详情
(XXXII)	59878	2-[(3R,4R,5R)-3,5-bis{[tert-butyl(diphenyl)silyl]oxy}-4-(3-{[tert-butyl(diphenyl)silyl]oxy}propoxy)-2-methylenecyclohexylidene]ethyl(diphenyl)phosphine oxide; {2-[(3R,4R,5R)-3,5-bis{[tert-butyl(diphenyl)silyl]oxy}-4-(3-{[tert-butyl(diphenyl)silyl]oxy}propoxy)-2-methylenecyclohexylidene]ethyl}(oxo)diphenylphosphorane	C₇₂H₈₃O₅PSi₃	详情	详情
(XXXIII)	59905	(1R,3aR,7aR)-1-{(1R)-1,5-dimethyl-5-[(triethylsilyl)oxy]hexyl}-7a-methyloctahydro-4H-inden-4-one	C₂₄H₄₆O₂Si	详情	详情
(XXXIV)	59879		C₈₁H₁₁₂O₅Si₄	详情	详情

合成路线3

该中间体在本合成路线中的序号：(XXX)

Basic hydrolysis of the pivalate esters of (XLV) followed by protection with tert-butyldimethylsilyl chloride provided the trisilylated derivative (XLVI). The p-methoxybenzyl protecting group of (XLVI) was then removed by treatment with DDQ, yielding (XLVII). Red-Al reduction of the propargyl alcohol (XLVII), followed by iodination produced the vinyl iodide (XLVIII). Intramolecular cyclization of iodide (XLVIII) under Heck reaction conditions gave rise to the key allyl alcohol intermediate (XXX), along with its undesired diastereoisomer (XLIX), which was separated by column chromatography

参考文献中间体

合成目标

【1】 Hatakeyama, S.; Ikeda, T.; Maeyama, J.; Esumi, T.; Iwabuchi, Y.; Irie, H.; Convergent synthesis of 1alpha, 25-dihydroxy-2beta-(3-hydroxypropoxy)vitamin D3 (ED-71). Bioorg Med Chem Lett 1997, 7, 22, 2871.

中间体序号	中间体编号	品名	分子式	供应商	用于合成
(XXX)	59876	2-[(3R,4R,5R)-3,5-bis{[tert-butyl(diphenyl)silyl]oxy}-4-(3-{[tert-butyl(diphenyl)silyl]oxy}propoxy)-2-methylenecyclohexylidene]-1-ethanol	C₆₀H₇₄O₅Si₃	详情	详情
(XLV)	59882	3-({(1R,2R)-1-{1-[(2,2-dimethylpropanoyl)oxy]-2-propenyl}-2-hydroxy-6-[(4-methoxybenzyl)oxy]-4-hexynyl}oxy)propyl pivalate	C₃₀H₄₄O₈	详情	详情
(XLVI)	59884	(5R,6R)-5,7-bis{[tert-butyl(dimethyl)silyl]oxy}-6-(3-{[tert-butyl(dimethyl)silyl]oxy}propoxy)-8-nonen-2-ynyl 4-methoxybenzyl ether; (6R)-6-{(1R)-1-{[tert-butyl(dimethyl)silyl]oxy}-5-[(4-methoxybenzyl)oxy]-3-pentynyl}-2,2,3,3,12,12,13,13-octamethyl-5-vinyl-4,7,11-trioxa-3,12-disilatetradecane	C₃₈H₇₀O₆Si₃	详情	详情
(XLVII)	59885	(5R,6R)-5,7-bis{[tert-butyl(dimethyl)silyl]oxy}-6-(3-{[tert-butyl(dimethyl)silyl]oxy}propoxy)-8-nonen-2-yn-1-ol	C₃₀H₆₂O₅Si₃	详情	详情
(XLVIII)	59886	(2Z,5R,6R)-5,7-bis{[tert-butyl(dimethyl)silyl]oxy}-6-(3-{[tert-butyl(dimethyl)silyl]oxy}propoxy)-3-iodo-2,8-nonadien-1-ol	C₃₀H₆₃IO₅Si₃	详情	详情
(XLIX)	59887	2-[(3S,4R,5R)-3,5-bis{[tert-butyl(diphenyl)silyl]oxy}-4-(3-{[tert-butyl(diphenyl)silyl]oxy}propoxy)-2-methylenecyclohexylidene]-1-ethanol	C₆₀H₇₄O₅Si₃	详情	详情

Extended Information