(2S)-2-methyl-6-hepten-1-ol -Drug Synthesis Database

【结构式】

【分子编号】27184

【品名】(2S)-2-methyl-6-hepten-1-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：(IX)

C7-C12 fragment.- The selective monoepoxidation of 1,7-octadiene (I) with m-chloroperbenzoic acid (MCPBA) gives the epoxide (II), which is oxidized with periodic acid to the aldehyde (III). Further oxidation of (III) by means of NaClO2 yields 6-heptenoic acid (IV), which is condensed with the lithium salt of the chiral oxazolidinone (V) by means of pivaloyl chloride affording the chiral imide (VI). The methylation of (VI) with methyl iodide and sodium hexamethyldisylazide (NaHMDS) in THF provides the methylated chiral imide (VII) as a single enantiomer. The hydrolysis of (VII) with H2O2 and LiOH gives the corresponding free acid (VIII), which is reduced with LiAlH4 to the primery alcohol (IX). Finally, (IX) is treated with Swern oxidant to afford the desired taret aldehyde (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)	27177	1,7-octadiene	3710-30-3	C₈H₁₄	详情	详情
(II)	27178	2-(5-hexenyl)oxirane	19600-63-6	C₈H₁₄O	详情	详情
(III)	27179	6-heptenal		C₇H₁₂O	详情	详情
(IV)	27180	6-heptenoic acid	1119-60-4	C₇H₁₂O₂	详情	详情
(V)	10793	[(4S)-4-Benzyl-2-oxo-1,3-oxazolidin-3-yl]lithium		C₁₀H₁₀LiNO₂	详情	详情
(VI)	27181	(4S)-4-benzyl-3-(6-heptenoyl)-1,3-oxazolidin-2-one		C₁₇H₂₁NO₃	详情	详情
(VII)	27182	(4S)-4-benzyl-3-[(2S)-2-methyl-6-heptenoyl]-1,3-oxazolidin-2-one		C₁₈H₂₃NO₃	详情	详情
(VIII)	27183	(2S)-2-methyl-6-heptenoic acid		C₈H₁₄O₂	详情	详情
(IX)	27184	(2S)-2-methyl-6-hepten-1-ol		C₈H₁₆O	详情	详情
(X)	27185	(2S)-2-methyl-6-heptenal		C₈H₁₄O	详情	详情

合成路线2

该中间体在本合成路线中的序号：(I)

The protection of 2(S)-methyl-6-hepten-1-ol (I) with Tes-Cl gives the silyl ether (II), which is oxidized by known methods to yield the aldehyde (III). The condensation of (III) with the acetylenic alcohol (IV) by means of Zn(OTf)2 and TEA to afford the acetylenic diol (V), which is selectively monobenzoylated with benzoyl chloride and TEA, providing the benzoate (VI). Extrusion of acetone from (VI) by means of K2CO3 in refluxing toluene gives the chiral octyne derivative (VII), which is reduced and debenzoylated with LiAlH4 in ethyl ether to yield the unsaturated alcohol (VIII). The condensation of (VIII) with the phosphonate (IX) by means of Et-MgBr affords the isoxazoline (X), which is treated with Tbdms-OTf and DIEA to provide the silyl ether (XI). The condensation of the phosphonate (XI) with 2-methylthiazole-4-carbaldehyde (XII) gives the adduct (XIII), which is treated with SmI2 to open the isoxazoline ring and yield the beta-hydroxy ketone (XIV). The reduction of (XIV) by means of BEt3 and NaBH4 affords the beta-diol (XV), which is treated with SOCl2 and TEA to provide the cyclic sulfite (XVI). The treatment of (XVI) with TBAF in refluxing THF/water gives the chiral epoxide (XVII), which is silylated with Tes-Cl and TEA to yield the bis silyl ether (XVIII). The selective deprotection of the primary silyl ether of (XVIII) by means of Ac-OH in THF/water affords the primary alcohol (XIX).

参考文献中间体

合成目标

【1】 Bode, J.W.; Carreira, E.M.; Stereoselective syntheses of epothilones A and B via nitrile oxide cycloadditions and related studies. J Org Chem 2001, 66, 19, 6410.

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)	27184	(2S)-2-methyl-6-hepten-1-ol		C₈H₁₆O	详情	详情
(II)	49304	triisopropyl[[(2S)-2-methyl-6-heptenyl]oxy]silane; (2S)-2-methyl-6-heptenyl triisopropylsilyl ether		C₁₇H₃₆OSi	详情	详情
(III)	49305	(5S)-5-methyl-6-[(triisopropylsilyl)oxy]hexanal		C₁₆H₃₄O₂Si	详情	详情
(IV)	17922	2-methyl-3-butyn-2-ol; 3-Methyl butynol	115-19-5	C₅H₈O	详情	详情
(V)	49306	(5R,9S)-2,9-dimethyl-10-[(triisopropylsilyl)oxy]-3-decyne-2,5-diol		C₂₁H₄₂O₃Si	详情	详情
(VI)	49307	(1R)-4-hydroxy-4-methyl-1-[(4S)-4-methyl-5-[(triisopropylsilyl)oxy]pentyl]-2-pentynyl benzoate		C₂₈H₄₆O₄Si	详情	详情
(VII)	60464	(1R)-1-{(4S)-4-methyl-5-[(triisopropylsilyl)oxy]pentyl}-2-propynyl benzoate		C₂₅H₄₀O₃Si	详情	详情
(VIII)	49308	(3R,7S)-7-methyl-8-[(triisopropylsilyl)oxy]-1-octen-3-ol		C₁₈H₃₈O₂Si	详情	详情
(IX)	60465			C₄H₈ClNO₄PT	详情	详情
(X)	60466			C₂₂H₄₅NO₆PSiT	详情	详情
(XI)	60467			C₂₈H₅₉NO₆PSi₂T	详情	详情
(XII)	44455	2-methyl-1,3-thiazole-4-carbaldehyde		C₅H₅NOS	详情	详情
(XIII)	49311	(5R)-5-[(1R,5S)-1-[[tert-butyl(dimethyl)silyl]oxy]-5-methyl-6-[(triisopropylsilyl)oxy]hexyl]-3-[(E)-1-methyl-2-(2-methyl-1,3-thiazol-4-yl)ethenyl]-4,5-dihydroisoxazole; tert-butyl(dimethyl)silyl (1R,5S)-5-methyl-1-[(5R)-3-[(E)-1-methyl-2-(2-methyl-1,3-thiazol-4-yl)ethenyl]-4,5-dihydro-5-isoxazolyl]-6-[(triisopropylsilyl)oxy]hexyl ether		C₃₂H₆₀N₂O₃SSi₂	详情	详情
(XIV)	60468	(E,5R,6R,10S)-6-{[tert-butyl(dimethyl)silyl]oxy}-5-hydroxy-2,10-dimethyl-1-(2-methyl-1,3-thiazol-4-yl)-11-[(triisopropylsilyl)oxy]-1-undecen-3-one		C₃₂H₆₁NO₄SSi₂	详情	详情
(XV)	49312	(E,3S,5R,6R,10S)-6-[[tert-butyl(dimethyl)silyl]oxy]-2,10-dimethyl-1-(2-methyl-1,3-thiazol-4-yl)-11-[(triisopropylsilyl)oxy]-1-undecene-3,5-diol		C₃₂H₆₃NO₄SSi₂	详情	详情
(XVI)	60469	(4R,6S)-4-{(1R,5S)-1-{[tert-butyl(dimethyl)silyl]oxy}-5-methyl-6-[(triisopropylsilyl)oxy]hexyl}-6-[(E)-1-methyl-2-(2-methyl-1,3-thiazol-4-yl)ethenyl]-1,3,2lambda~4~-dioxathian-2-one		C₃₂H₆₁NO₅S₂Si₂	详情	详情
(XVII)	60470	(2S,3E)-1-{(2S,3R)-3-[(4S)-5-hydroxy-4-methylpentyl]oxiranyl}-3-methyl-4-(2-methyl-1,3-thiazol-4-yl)-3-buten-2-ol		C₁₇H₂₇NO₃S	详情	详情
(XVIII)	60471	(2S)-2-methyl-5-((2R,3S)-3-{(2S,3E)-3-methyl-4-(2-methyl-1,3-thiazol-4-yl)-2-[(triethylsilyl)oxy]-3-butenyl}oxiranyl)pentyl triethylsilyl ether; 2-methyl-4-{(E,3S)-2-methyl-4-((2S,3R)-3-{(4S)-4-methyl-5-[(triethylsilyl)oxy]pentyl}oxiranyl)-3-[(triethylsilyl)oxy]-1-butenyl}-1,3-thiazole		C₂₉H₅₅NO₃SSi₂	详情	详情
(XIX)	49315	(2S)-2-methyl-5-((2R,3S)-3-[(2S,3E)-3-methyl-4-(2-methyl-1,3-thiazol-4-yl)-2-[(triethylsilyl)oxy]-3-butenyl]oxiranyl)-1-pentanol		C₂₃H₄₁NO₃SSi	详情	详情

Extended Information