2-ethyl-2-propen-1-ol -Drug Synthesis Database

【结构式】

【分子编号】63603

【品名】2-ethyl-2-propen-1-ol

【CA登记号】

【分子式】C₅H₁₀O

【分子量】86.1338

【元素组成】C 69.72% H 11.7% O 18.58%

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：(I)

In an alternative synthesis, which does not utilize the alkaloid catharanthine, Sharpless asymmetric epoxidation of 2-ethyl-2-propenol (I) in the presence of ( )-diethyl tartrate provides (R)-2-ethyl-2,3-epoxypropanol (II). Subsequent addition of allylmagnesium chloride (III) to epoxide (II) leads to diol (IV), which is further protected as the corresponding acetonide (V) with 2,2 dimethoxypropane and p-TsOH. Ozonolysis of the terminal olefin (V) gives rise to aldehyde (VI). Condensation of aldehyde (VI) with the indoloazapine (VII) furnishes the bridged azepine (VIII) as a diastereomeric mixture. Without isolation, this mixture of amines is N-alkylated with benzyl bromide, and the resultant ammonium salts (IX) are subjected to rearrangement in boiling MeOH in the presence of Et3N to provide an equimolecular mixture of the tetracyclic diastereoisomers (X) and (XI) (5).

参考文献中间体

合成目标

【1】 Kuehne, M.E.; Matson, P.A..; Bornmann, W.G.; Enantioselective syntheses of vinblastine, leurosidine, vincovaline, and 20'-epi-vincovaline. J Org Chem 1991, 56, 2, 513.

中间体序号	中间体编号	品名	分子式	供应商	用于合成
(I)	63603	2-ethyl-2-propen-1-ol	C₅H₁₀O	详情	详情
(II)	63604	(2-ethyl-2-oxiranyl)methanol	C₅H₁₀O₂	详情	详情
(III)	61128		C₄H₈	详情	详情
(IV)	63605	2-ethyl-5-hexene-1,2-diol	C₈H₁₆O₂	详情	详情
(V)	63606	4-(3-butenyl)-4-ethyl-2,2-dimethyl-1,3-dioxolane	C₁₁H₂₀O₂	详情	详情
(VI)	63607	3-(4-ethyl-2,2-dimethyl-1,3-dioxolan-4-yl)propanal	C₁₀H₁₈O₃	详情	详情
(VII)	63608	methyl 1,2,3,4,5,6-hexahydroazepino[4,5-b]indole-5-carboxylate	C₁₄H₁₆N₂O₂	详情	详情
(VIII)	63609	methyl 15-{2-[(4S)-4-ethyl-2,2-dimethyl-1,3-dioxolan-4-yl]ethyl}-8,12-diazatetracyclo[10.2.1.0~1,9~.0~2,7~]pentadeca-2,4,6,9-tetraene-10-carboxylate	C₂₄H₃₂N₂O₄	详情	详情
(IX)	63610	12-benzyl-15-{2-[(4S)-4-ethyl-2,2-dimethyl-1,3-dioxolan-4-yl]ethyl}-10-(methoxycarbonyl)-8-aza-12-azoniatetracyclo[10.2.1.0~1,9~.0~2,7~]pentadeca-2,4,6,9-tetraene bromide	C₃₁H₃₉BrN₂O₄	详情	详情
(X)	63611	methyl 4-[(4-ethyl-2,2-dimethyl-1,3-dioxolan-4-yl)methyl]-3-(phenylmethyl)-2,3,3a,4,5,7-hexahydro-1H-pyrrolo[2,3-d]carbazole-6-carboxylate	C₃₁H₃₈N₂O₄	详情	详情
(XI)	63612	methyl 4-[(4-ethyl-2,2-dimethyl-1,3-dioxolan-4-yl)methyl]-3-(phenylmethyl)-2,3,3a,4,5,7-hexahydro-1H-pyrrolo[2,3-d]carbazole-6-carboxylate	C₃₁H₃₈N₂O₄	详情	详情

合成路线2

该中间体在本合成路线中的序号：(XI)

In an alternative, stereospecific synthesis of (X), Sharpless asymmetric epoxidation of 2-ethyl-2-propen-1-ol (XI) in the presence of (-)-diethyl tartrate provides the (R)-epoxide (XII). Ring opening of (XII) with sodium thiophenoxide produces diol (XIII), which is further protected with 1-methoxycyclohexene (VII), yielding ketal (XIV). Sulfide (XIV) is then oxidized with mCPBA to afford sulfoxide (XV) as a mixture of diastereoisomers. Pummerer rearrangement of sulfoxides (XV) in boiling Ac2O, followed by alkaline hydrolysis of the intermediate alpha-acetoxy sulfides furnishes aldehyde (XVI). Then, aldol condensation of aldehyde (XVI) with thiolactam (I) employing stannous triflate and N-ethylpiperidine gives adduct (XVII). Dehydration of alcohol (XVII) to the alpha,beta-unsaturated thiolactam (XVIII) is accomplished by tosylation with p-toluenesulfonic anhydride, followed by tosylate elimination in the presence of DBU. Desulfuration of thiolactam (XVIII) with deactivated Ra-Ni leads to (XIX). Then, hydrogenation of olefin (XIX) produces a mixture of epimers, from which the target isomer (X) can be isolated by column chromatography (7).

参考文献中间体

合成目标

【1】 Magnus, P.; Mendoza, J.S.; Stamford, A.; Ladlow, M.; Willis, P.; Nonoxidative coupling methodology for the synthesis of the antitumor bisindole alkaloid vinblastine and a lower-half analogue: Solvent effect on the stereochemistry of the crucial C-15/C-18' bond. J Am Chem Soc 1992, 114, 26, 10232.

中间体序号	中间体编号	品名	分子式	供应商	用于合成
(I)	63624	methyl 3-thioxo-2,3,6,11-tetrahydro-1H-indolizino[8,7-b]indole-11b(5H)-carboxylate	C₁₆H₁₆N₂O₂S	详情	详情
(VII)	63630	1-(methyloxy)-1-cyclohexene; 1-cyclohexen-1-yl methyl ether	C₇H₁₂O	详情	详情
(X)	63633	methyl 2-[(2-ethyl-1,4-dioxaspiro[4.5]dec-2-yl)methyl]-2,3,6,11-tetrahydro-1H-indolizino[8,7-b]indole-11b(5H)-carboxylate	C₂₇H₃₆N₂O₄	详情	详情
(XI)	63603	2-ethyl-2-propen-1-ol	C₅H₁₀O	详情	详情
(XII)	63604	(2-ethyl-2-oxiranyl)methanol	C₅H₁₀O₂	详情	详情
(XIII)	63634	2-[(phenylsulfanyl)methyl]-1,2-butanediol	C₁₁H₁₆O₂S	详情	详情
(XIV)	63635	2-ethyl-2-[(phenylsulfanyl)methyl]-1,4-dioxaspiro[4.5]decane; (2-ethyl-1,4-dioxaspiro[4.5]dec-2-yl)methyl phenyl sulfide	C₁₇H₂₄O₂S	详情	详情
(XV)	63636	(2-ethyl-1,4-dioxaspiro[4.5]dec-2-yl)methyl phenyl sulfoxide; 2-ethyl-2-[(phenylsulfinyl)methyl]-1,4-dioxaspiro[4.5]decane	C₁₇H₂₄O₃S	详情	详情
(XVI)	63637		C₁₁H₁₈O₃	详情	详情
(XVII)	63638	methyl 2-[(2-ethyl-1,4-dioxaspiro[4.5]dec-2-yl)(hydroxy)methyl]-3-thioxo-2,3,6,11-tetrahydro-1H-indolizino[8,7-b]indole-11b(5H)-carboxylate	C₂₇H₃₄N₂O₅S	详情	详情
(XVIII)	63639	methyl 2-[(2-ethyl-1,4-dioxaspiro[4.5]dec-2-yl)methylidene]-3-thioxo-2,3,6,11-tetrahydro-1H-indolizino[8,7-b]indole-11b(5H)-carboxylate	C₂₇H₃₂N₂O₄S	详情	详情
(XIX)	63640	methyl 2-[(2-ethyl-1,4-dioxaspiro[4.5]dec-2-yl)methylidene]-2,3,6,11-tetrahydro-1H-indolizino[8,7-b]indole-11b(5H)-carboxylate	C₂₇H₃₄N₂O₄	详情	详情

Extended Information