(3R)-4,4-dimethyl-5-hexen-3-ol -Drug Synthesis Database

【结构式】

【分子编号】27172

【品名】(3R)-4,4-dimethyl-5-hexen-3-ol

【CA登记号】

【分子式】C₈H₁₆O

【分子量】128.21444

【元素组成】C 74.94% H 12.58% O 12.48%

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：(IV)

C1-C6 fragment.- The reaction of 3-methyl-2-butenylmagnesium chloride (I) with propanal (II) gives racemic 4,4-dimethyl-5-hexen-3-ol (III), which was submitted to enzymatic resolution with ChiroCLEC-PC dry enzyme yielding the (R) enantiomer (IV). The esterification of (IV) with bromoacetyl bromide (V) and dimethylaniline yields the corresponding ester (VI), which is oxidized with O3 and trimethyl phosphite and cyclized with SmI2 in THF to afford chiral tetrahydropyran-2-one (VII). The reduction of (VII) with Red-Al, followed by cyclization with 2-methoxypropene (VIII) and PPTS yields the acetonide (IX), which is finally oxidized with N-methylmorpholine-N-oxide and PPTS in dichloromethane giving the target intermediate (X).

参考文献中间体

合成目标

【1】 Taylor, R.E.; et al.; A formal total synthesis of epothiolone A: Enantioselective preparation of the C1-C6 and C7-C12 fragments. J Org Chem 1998, 63, 25, 9580.

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)	27170	chloro(3-methyl-2-butenyl)magnesium		C₅H₉ClMg	详情	详情
(II)	15966	propionaldehyde	123-38-6	C₃H₆O	详情	详情
(III)	27171	4,4-dimethyl-5-hexen-3-ol		C₈H₁₆O	详情	详情
(IV)	27172	(3R)-4,4-dimethyl-5-hexen-3-ol		C₈H₁₆O	详情	详情
(V)	14005	2-Bromoacetyl bromide; Bromoacetyl bromide	598-21-0	C₂H₂Br₂O	详情	详情
(VI)	27173	(1R)-1-ethyl-2,2-dimethyl-3-butenyl 2-bromoacetate		C₁₀H₁₇BrO₂	详情	详情
(VII)	27174	(4S,6R)-6-ethyl-4,5,5-trimethyltetrahydro-2H-pyran-2-one		C₁₀H₁₈O₂	详情	详情
(VIII)	17354	isopropenyl methyl ether; 2-methoxy-1-propene	116-11-0	C₄H₈O	详情	详情
(IX)	27175	(3R)-2-[(4S)-2,2-dimethyl-1,3-dioxan-4-yl]-2-methyl-3-pentanol		C₁₂H₂₄O₃	详情	详情
(X)	27176	2-[(4S)-2,2-dimethyl-1,3-dioxan-4-yl]-2-methyl-3-pentanone		C₁₂H₂₂O₃	详情	详情

合成路线2

该中间体在本合成路线中的序号：(XIX)

The reaction of 3-methyl-2-butenylmagnesium bromide (XVI) with propanal (XVII) gives racemic hexenol (XVIII), which is submitted to enzymatic resolution with ChiroCLEC-PC dry enzyme, yielding the R-enantiomer (XIX). The esterification of (XIX) with bromoacetyl bromide (XX) and dimethylaniline (DMA) affords the corresponding ester (XXI), which is oxidized with O3 and trimethyl phosphite and cyclized with SmI2 in THF to provide the chiral tetrahydropyranone (XXII). The reduction of (XXII) with Red-Al, followed by cyclization with 2-methoxypropene (XXIII) and PPTS, gives the acetonide (XXIV), which is oxidized with PPTS and NMO to provide the protected dihydroxyketone (XXV). The condensation of the ketone (XXV) with 2(S)-methyl-6-heptenal (XXVI) by means of LDA in THF gives the hydroxyundecenone (XXVII), which is treated with pyridinium p-toluenesulfonate (PPTS) in methanol to cleave the 1,3-dioxane ring and yield the trihydroxy compound (XXVIII). The silylation of (XXVIII) with Tbdms-OTf and lutidine in dichloromethane affords the fully silylated compound (XXIX), which is selectively monodesilylated with CSA to provide the primary alcohol (XXX). Finally, this alcohol is oxidized by means of pyridinium dichromate (PDC) in DMF to furnish the target tridecenoic acid intermediate (XII).

参考文献中间体

合成目标

【1】 Schinzer, D.; et al.; Total synthesis of (-)-epothilone A. Angew Chem. Int Ed Engl 1997, 36, 5, 523.
【2】 Taylor, R.E.; et al.; A formal total synthesis of epothiolone A: Enantioselective preparation of the C1-C6 and C7-C12 fragments. J Org Chem 1998, 63, 25, 9580.

中间体序号	中间体编号	品名	CAS号	分子式	供应商	用于合成
(XVI)	27170	chloro(3-methyl-2-butenyl)magnesium		C₅H₉ClMg	详情	详情
(XVII)	15966	propionaldehyde	123-38-6	C₃H₆O	详情	详情
(XVIII)	27171	4,4-dimethyl-5-hexen-3-ol		C₈H₁₆O	详情	详情
(XIX)	27172	(3R)-4,4-dimethyl-5-hexen-3-ol		C₈H₁₆O	详情	详情
(XX)	14005	2-Bromoacetyl bromide; Bromoacetyl bromide	598-21-0	C₂H₂Br₂O	详情	详情
(XXI)	27173	(1R)-1-ethyl-2,2-dimethyl-3-butenyl 2-bromoacetate		C₁₀H₁₇BrO₂	详情	详情
(XXII)	27174	(4S,6R)-6-ethyl-4,5,5-trimethyltetrahydro-2H-pyran-2-one		C₁₀H₁₈O₂	详情	详情
(XXIII)	17354	isopropenyl methyl ether; 2-methoxy-1-propene	116-11-0	C₄H₈O	详情	详情
(XXIV)	27175	(3R)-2-[(4S)-2,2-dimethyl-1,3-dioxan-4-yl]-2-methyl-3-pentanol		C₁₂H₂₄O₃	详情	详情
(XXV)	27176	2-[(4S)-2,2-dimethyl-1,3-dioxan-4-yl]-2-methyl-3-pentanone		C₁₂H₂₂O₃	详情	详情
(XXVI)	27185	(2S)-2-methyl-6-heptenal		C₈H₁₄O	详情	详情
(XXVII)	44434	(4R,5S,6S)-2-[(4S)-2,2-dimethyl-1,3-dioxan-4-yl]-5-hydroxy-2,4,6-trimethyl-10-undecen-3-one		C₂₀H₃₆O₄	详情	详情
(XXVIII)	44435	(3S,6R,7S,8S)-1,3,7-trihydroxy-4,4,6,8-tetramethyl-12-tridecen-5-one		C₁₇H₃₂O₄	详情	详情
(XXIX)	44436	(5S,6R,9S)-9-[[tert-butyl(dimethyl)silyl]oxy]-2,2,3,3,6,8,8,13,13,14,14-undecamethyl-5-[(1S)-1-methyl-5-hexenyl]-4,12-dioxa-3,13-disilapentadecan-7-one		C₃₅H₇₄O₄Si₃	详情	详情
(XXX)	44437	(5S,8R,9S)-5-(2-hydroxyethyl)-2,2,3,3,6,6,8,11,11,12,12-undecamethyl-9-[(1S)-1-methyl-5-hexenyl]-4,10-dioxa-3,11-disilatridecan-7-one		C₂₉H₆₀O₄Si₂	详情	详情
(XXX)	44438	(3S,6R,7S,8S)-3,7-bis[[tert-butyl(dimethyl)silyl]oxy]-4,4,6,8-tetramethyl-5-oxo-12-tridecenoic acid		C₂₉H₅₈O₅Si₂	详情	详情

Extended Information