tert-butyl(dimethyl)silyl (1S,2R)-3-iodo-1-[(1R)-1-[(4S,5S)-2-(4-methoxyphenyl)-5-methyl-1,3-dioxan-4-yl]ethyl]-2-methylpropyl ether; tert-butyl[((1S,2R)-3-iodo-1-[(1R)-1-[(4S,5S)-2-(4-methoxyphenyl)-5-methyl-1,3-dioxan-4-yl]ethyl]-2-methylpropyl)oxy]dimethylsilane -Drug Synthesis Database

【结构式】

【分子编号】42665

【品名】tert-butyl(dimethyl)silyl (1S,2R)-3-iodo-1-[(1R)-1-[(4S,5S)-2-(4-methoxyphenyl)-5-methyl-1,3-dioxan-4-yl]ethyl]-2-methylpropyl ether; tert-butyl[((1S,2R)-3-iodo-1-[(1R)-1-[(4S,5S)-2-(4-methoxyphenyl)-5-methyl-1,3-dioxan-4-yl]ethyl]-2-methylpropyl)oxy]dimethylsilane

【CA登记号】

【分子式】C₂₄H₄₁IO₄Si

【分子量】548.57711

【元素组成】C 52.55% H 7.53% I 23.13% O 11.67% Si 5.12%

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：(XV)

The intermediate (XV) has been obtained as follows: The reaction of methyl 3-hydroxy-2(S)-methylpropionate (I) with 4-methoxybenzyl trichloroacetimidate gives methyl 3-(4-methoxybenzyloxy)-2(S)-methylpropionate (II), which is reduced with LiAlH4, yielding the primary alcohol (III). The Swern oxidation of (III) affords the aldehyde (IV), which is condensed with the chiral imidazolidinone (V) to provide the adduct (VI). The transamidation of (VI) with N,O-dimethylhydroxylamine by means of Me3Al gives the methoxyamide (VII), which is debenzylated with DDQ to yield the diol (VIII). The reaction of (VIII) with 4-methoxybenzaldehyde diethylacetal (IX) and CSA affords the cyclic ketal (X), which is condensed with the propionyloxazolidinone (XI) by means of dibutylboron triflate to furnish the adduct (XII). The silylation of the OH group of (XII) with Tbdms-OTf gives the silyl ether (XIII), which is reduced at the amide group with LiBH4 to yield the primary alcohol (XIV). Finally, this compound is treated with I2 and PPH3 to afford the intermediate iodo derivative (XV).

参考文献中间体

合成目标

【1】 Smith, A.B. III; et al.; Gram-scale synthesis of (+)-discodermolide. Org Lett 1999, 1, 11, 1823.
【2】 Smith, A.B. III; et al.; Evolution of a gram-scale synthesis of (+)-discodermolide. J Am Chem Soc 2000, 122, 36, 8654.

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)	17128	Methyl (2S)-3-hydroxy-2-methylpropanoate	72657-23-9	C₅H₁₀O₃	详情	详情
(II)	42654	methyl (2S)-3-[(4-methoxybenzyl)oxy]-2-methylpropanoate		C₁₃H₁₈O₄	详情	详情
(III)	42655	(2R)-3-[(4-methoxybenzyl)oxy]-2-methyl-1-propanol		C₁₂H₁₈O₃	详情	详情
(IV)	42656	(2S)-3-[(4-methoxybenzyl)oxy]-2-methylpropanal		C₁₂H₁₆O₃	详情	详情
(V)	42657	(4R,5S)-3-[(Z)-1-butoxy-1-propenyl]-4-methyl-5-phenyl-1,3-oxazolidin-2-one		C₁₇H₂₃NO₃	详情	详情
(VI)	42658	(4R,5S)-3-[(2R,3S,4S)-3-hydroxy-5-[(4-methoxybenzyl)oxy]-2,4-dimethylpentanoyl]-4-methyl-5-phenyl-1,3-oxazolidin-2-one		C₂₅H₃₁NO₆	详情	详情
(VII)	42659	(2R,3S,4S)-3-hydroxy-N-methoxy-5-[(4-methoxybenzyl)oxy]-N,2,4-trimethylpentanamide		C₁₇H₂₇NO₅	详情	详情
(VIII)	42660	(2R,3S,4S)-3,5-dihydroxy-N-methoxy-N,2,4-trimethylpentanamide		C₉H₁₉NO₄	详情	详情
(IX)	35670	1-(diethoxymethyl)-4-methoxybenzene; 4-(diethoxymethyl)phenyl methyl ether		C₁₂H₁₈O₃	详情	详情
(X)	42661	(2R)-N-methoxy-2-[(4S,5S)-2-(4-methoxyphenyl)-5-methyl-1,3-dioxan-4-yl]-N-methylpropanamide		C₁₇H₂₅NO₅	详情	详情
(XI)	10968	(4R)-3-Acetyl-4-benzyl-1,3-oxazolidin-2-one; (R)-(-)-3-Acetyl-4-benzyl-2-oxazolidinone	184363-65-3	C₁₂H₁₃NO₃	详情	详情
(XII)	42662	(4R)-4-benzyl-3-[(2R,3S,4S)-3-hydroxy-4-[(4S,5S)-2-(4-methoxyphenyl)-5-methyl-1,3-dioxan-4-yl]-2-methylpentanoyl]-1,3-oxazolidin-2-one		C₂₈H₃₅NO₇	详情	详情
(XIII)	42663	(4R)-4-benzyl-3-[(2R,3S,4R)-3-[[tert-butyl(dimethyl)silyl]oxy]-4-[(4S,5S)-2-(4-methoxyphenyl)-5-methyl-1,3-dioxan-4-yl]-2-methylpentanoyl]-1,3-oxazolidin-2-one		C₃₄H₄₉NO₇Si	详情	详情
(XIV)	42664	(2S,3R,4R)-3-[[tert-butyl(dimethyl)silyl]oxy]-4-[(4S,5S)-2-(4-methoxyphenyl)-5-methyl-1,3-dioxan-4-yl]-2-methyl-1-pentanol		C₂₄H₄₂O₅Si	详情	详情
(XV)	42665	tert-butyl(dimethyl)silyl (1S,2R)-3-iodo-1-[(1R)-1-[(4S,5S)-2-(4-methoxyphenyl)-5-methyl-1,3-dioxan-4-yl]ethyl]-2-methylpropyl ether; tert-butyl[((1S,2R)-3-iodo-1-[(1R)-1-[(4S,5S)-2-(4-methoxyphenyl)-5-methyl-1,3-dioxan-4-yl]ethyl]-2-methylpropyl)oxy]dimethylsilane		C₂₄H₄₁IO₄Si	详情	详情

合成路线2

该中间体在本合成路线中的序号：(XV)

The target compound has been obtained as follows: The reaction of intermediate iodo derivative (XV) with ZnCl2 and BuLi gives the organozinc compound (XXVI), which is condensed with intermediate iodo derivative (XVIII) by means of Pd(PPh3)4, yielding the adduct (XXVII). The selective deprotection of the Pmb group of (XXVII) with DDQ, followed by reprotection with Tr-Cl, affords the suitably protected adduct (XXVIII). Cleaving of the cyclic ketal group of (XXVIII) with DIBAL provides the primary alcohol (XXIX), which is oxidized with DMP, giving the aldehyde (XXX). The condensation of (XXX) with the titanium derivative (XXXI) yields the adduct (XXXII), which is selectively deprotected at the trityl group with chloro-catecholborane to afford the primary alcohol (XXXIII). The reaction of (XXXIII) with PPh3 , I2 and DIEA furnishes the phosphonium iodide (XXXIV).

参考文献中间体

合成目标

【1】 Smith, A.B. III; et al.; Evolution of a gram-scale synthesis of (+)-discodermolide. J Am Chem Soc 2000, 122, 36, 8654.
【2】 Smith, A.B. III; et al.; Gram-scale synthesis of (+)-discodermolide. Org Lett 1999, 1, 11, 1823.

中间体序号	中间体编号	品名	分子式	供应商	用于合成
(XV)	42665	tert-butyl(dimethyl)silyl (1S,2R)-3-iodo-1-[(1R)-1-[(4S,5S)-2-(4-methoxyphenyl)-5-methyl-1,3-dioxan-4-yl]ethyl]-2-methylpropyl ether; tert-butyl[((1S,2R)-3-iodo-1-[(1R)-1-[(4S,5S)-2-(4-methoxyphenyl)-5-methyl-1,3-dioxan-4-yl]ethyl]-2-methylpropyl)oxy]dimethylsilane	C₂₄H₄₁IO₄Si	详情	详情
(XVIII)	42668	tert-butyl(dimethyl)silyl (1R,2S,3Z)-4-iodo-1-[(1S)-2-[(4-methoxybenzyl)oxy]-1-methylethyl]-2-methyl-3-pentenyl ether; tert-butyl[((1R,2S,3Z)-4-iodo-1-[(1S)-2-[(4-methoxybenzyl)oxy]-1-methylethyl]-2-methyl-3-pentenyl)oxy]dimethylsilane	C₂₃H₃₉IO₃Si	详情	详情
(XXVI)	42676	tert-butyl[(2R,3S,4R)-3-[[tert-butyl(dimethyl)silyl]oxy]-4-[(4S,5S)-2-(4-methoxyphenyl)-5-methyl-1,3-dioxan-4-yl]-2-methylpentyl]zinc	C₂₈H₅₀O₄SiZn	详情	详情
(XXVII)	42677	(5R,6S,7Z,10S,11R)-5-[(1S)-2-[(4-methoxybenzyl)oxy]-1-methylethyl]-11-[(1R)-1-[(4S,5S)-2-(4-methoxyphenyl)-5-methyl-1,3-dioxan-4-yl]ethyl]-2,2,3,3,6,8,10,13,13,14,14-undecamethyl-4,12-dioxa-3,13-disila-7-pentadecene; 4-((4S,5S)-4-[(1R,2R,3S,5Z,7S,8R,9S)-2,8-bis[[tert-butyl(dimethyl)silyl]oxy]-10-[(4-methoxybenzyl)oxy]-1,3,5,7,9-pentamethyl-5-decenyl]-5-methyl-1,3-dioxan-2-yl)phenyl methyl ether	C₄₇H₈₀O₇Si₂	详情	详情
(XXVIII)	42678	(5R,6S,7Z,10S,11R)-11-[(1R)-1-[(4S,5S)-2-(4-methoxyphenyl)-5-methyl-1,3-dioxan-4-yl]ethyl]-2,2,3,3,6,8,10,13,13,14,14-undecamethyl-5-[(1S)-1-methyl-2-(trityloxy)ethyl]-4,12-dioxa-3,13-disila-7-pentadecene; (2S,3R,4S,5Z,8S,9R,10R)-3,9-bis[[tert-butyl(dimethyl)silyl]oxy]-10-[(4S,5S)-2-(4-methoxyphenyl)-5-methyl-1,3-dioxan-4-yl]-2,4,6,8-tetramethyl-5-undecenyl trityl ether	C₅₈H₈₆O₆Si₂	详情	详情
(XXIX)	42679	(2S,3S,4R,5R,6S,8Z,10S,11R,12S)-5,11-bis[[tert-butyl(dimethyl)silyl]oxy]-3-[(4-methoxybenzyl)oxy]-2,4,6,8,10,12-hexamethyl-13-(trityloxy)-8-tridecen-1-ol	C₅₈H₈₈O₆Si₂	详情	详情
(XXX)	42680	(2R,3R,4R,5R,6S,8Z,10S,11R,12S)-5,11-bis[[tert-butyl(dimethyl)silyl]oxy]-3-[(4-methoxybenzyl)oxy]-2,4,6,8,10,12-hexamethyl-13-(trityloxy)-8-tridecenal	C₅₈H₈₆O₆Si₂	详情	详情
(XXXI)	42681		C₃₉H₃₄LiO₄PTi	详情	详情
(XXXII)	42682	(2S,3R,4S,5Z,8S,9R,10R,11S,12S,13Z)-3,9-bis[[tert-butyl(dimethyl)silyl]oxy]-11-[(4-methoxybenzyl)oxy]-2,4,6,8,10,12-hexamethyl-5,13,15-hexadecatrienyl trityl ether; (5R,6S,7Z,10S,11R)-11-[(1R,2S,3S,4Z)-2-[(4-methoxybenzyl)oxy]-1,3-dimethyl-4,6-heptadienyl]-2,2,3,3,6,8,10,13,13,14,14-undecamethyl-5-[(1S)-1-methyl-2-(trityloxy)ethyl]-4,12-dioxa-3,13-disila-7-pentadecene	C₆₁H₉₀O₅Si₂	详情	详情
(XXXIII)	42683	(2S,3R,4S,5Z,8S,9R,10R,11S,12S,13Z)-3,9-bis[[tert-butyl(dimethyl)silyl]oxy]-11-[(4-methoxybenzyl)oxy]-2,4,6,8,10,12-hexamethyl-5,13,15-hexadecatrien-1-ol	C₄₂H₇₆O₅Si₂	详情	详情
(XXXIV)	42684	[(2R,3R,4S,5Z,8S,9R,10R,11S,12S,13Z)-3,9-bis[[tert-butyl(dimethyl)silyl]oxy]-11-[(4-methoxybenzyl)oxy]-2,4,6,8,10,12-hexamethyl-5,13,15-hexadecatrienyl](triphenyl)phosphonium iodide	C₆₀H₉₀IO₄PSi₂	详情	详情

Extended Information