(2E,4E,6E)-2,7-dimethyl-2,4,6-octatrienedial -Drug Synthesis Database

【结构式】

【分子编号】39583

【品名】(2E,4E,6E)-2,7-dimethyl-2,4,6-octatrienedial

【CA登记号】

【分子式】C₁₀H₁₂O₂

【分子量】164.20408

【元素组成】C 73.15% H 7.37% O 19.49%

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)

The reaction of 3-methyl-2-trans-penten-4-yn-1-ol (I) with ethyl vinyl ether (II) by means of p-toluenesulfonic acid gives 1-(1-ethoxyethoxy)-3-methyl-4-trans-penten-1-yne (III), which is condensed with 2,6,6-trimethyl-3-isobutoxycyclohex-2-en-1-one (IV) by means of butyllithium in ether at -60 C to afford 5-(2,6,6-trimethyl-3-oxocyclohexen-1-yl)-3-methyl-2-trans-penten-4-yn-1-ol (V). The reduction of (V) with H2 over a Lindlar catalyst in toluene yields 5-(2,6,6-trimethyl-3-oxocyclohexen-1-yl)-3-methyl-2,4-pentadien-1-ol (VI), which is converted into the corresponding pentadienyl bromide (VII) by reaction with PBr3 in ether. The reaction of (VII) with triphenylphosphine in refluxing benzene affords 5-(2,6,6-trimethyl-3-oxocyclohexen-1-yl)-3-methyl-2,4-pentadien-1-triphenylphosphonium bromide (VIII) , which is finally condensed in a Wittig reaction with 2,7-dimethyl-2,4,6-octatriene-1,8-dial (IX) by means of sodium methoxide in dichloromethane.

参考文献中间体

合成目标

【1】 Serradell, M.N.; Blancafort, P.; Castaner, J.; Hillier, K.; Canthazanthin. Drugs Fut 1979, 4, 7, 477.
【2】 Rosenberg, M.; US 4000198 .
【3】 Rigassi, N.; Schwieter, U.; DE 2037935 .

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)	39576	(E)-3-methyl-2-penten-4-yn-1-ol	6153-06-6	C₆H₈O	详情	详情
(II)	18762	1-Ethoxyethylene; Ethyl vinyl ether；Ethoxyethene	109-92-2	C₄H₈O	详情	详情
(III)	39577	5-(1-ethoxyethoxy)-3-methyl-1-penten-4-yne; 1-ethoxyethyl 3-methyl-4-penten-1-ynyl ether		C₁₀H₁₆O₂	详情	详情
(IV)	39578	3-isobutoxy-2,6,6-trimethyl-2-cyclohexen-1-one		C₁₃H₂₂O₂	详情	详情
(V)	39579	3-[(E)-5-hydroxy-3-methyl-3-penten-1-ynyl]-2,4,4-trimethyl-2-cyclohexen-1-one		C₁₅H₂₀O₂	详情	详情
(VI)	39580	3-[(1E,3E)-5-hydroxy-3-methyl-1,3-pentadienyl]-2,4,4-trimethyl-2-cyclohexen-1-one	29538-78-1	C₁₅H₂₂O₂	详情	详情
(VII)	39581	3-[(1E,3E)-5-bromo-3-methyl-1,3-pentadienyl]-2,4,4-trimethyl-2-cyclohexen-1-one		C₁₅H₂₁BrO	详情	详情
(VIII)	39582	[(2E,4E)-3-methyl-5-(2,6,6-trimethyl-3-oxo-1-cyclohexen-1-yl)-2,4-pentadienyl](triphenyl)phosphonium bromide		C₃₃H₃₆BrOP	详情	详情
(IX)	39583	(2E,4E,6E)-2,7-dimethyl-2,4,6-octatrienedial		C₁₀H₁₂O₂	详情	详情

合成路线2

该中间体在本合成路线中的序号：(IX)

The reaction of beta-ionon (X) with triethyl orthoformate (A) by means of H2SO4 in dioxane gives beta-ionon enolether (XI), which by reaction with NBS in CCl4 and hydrolysis with acetic acid is converted into 4-acetoxyonon (XII). The Grignard reaction of (XII) with vinylmagnesium bromide (B) in THF and hydrolysis with KOH in methanol gives 5-(3-hydroxy-2,6,6-trimethylcyclohex-1-en-1-yl)-3-methylpenta-1,4-dien-3-ol (XIII), which is oxidized with MnO2 in methylene chloride yielding 5-(3-oxo-2,6,6-trimethylcyclohex-1-en-1-yl)-3-methylpenta-1,4-dien-3-ol (XIV). Finally, this compound by reaction with triphenylphosphonium bromide (C) in DMF is converted into the phosphonium salt (VIII), which is finally condensed in a Wittig reaction with 2,7-dimethyl-2,4,6-octatriene-1,8-dial (IX) by means of sodium methoxide in dichloromethane.

参考文献中间体

合成目标

【1】 Rosenberg, M.; US 4000198 .
【2】 Serradell, M.N.; Blancafort, P.; Castaner, J.; Hillier, K.; Canthazanthin. Drugs Fut 1979, 4, 7, 477.
【3】 Rigassi, N.; Schwieter, U.; DE 2037935 .

中间体序号	中间体编号	品名	CAS号	分子式	供应商	用于合成
(B)	16524	bromo(vinyl)magnesium	1826-67-1	C₂H₃BrMg	详情	详情
(A)	21304	Triethyl orthoformate; 1-(Diethoxymethoxy)ethane; Diethoxymethyl ethyl ether	122-51-0	C₇H₁₆O₃	详情	详情
(VIII)	39582	[(2E,4E)-3-methyl-5-(2,6,6-trimethyl-3-oxo-1-cyclohexen-1-yl)-2,4-pentadienyl](triphenyl)phosphonium bromide		C₃₃H₃₆BrOP	详情	详情
(IX)	39583	(2E,4E,6E)-2,7-dimethyl-2,4,6-octatrienedial		C₁₀H₁₂O₂	详情	详情
(X)	39584	(E)-4-(2,6,6-trimethyl-1-cyclohexen-1-yl)-3-buten-2-one	14901-07-6	C₁₃H₂₀O	详情	详情
(XI)	39585	6-[(Z,2Z)-3-methoxy-2-butenylidene]-1,5,5-trimethyl-1-cyclohexene; methyl (Z)-1-methyl-3-(2,6,6-trimethyl-2-cyclohexen-1-ylidene)-1-propenyl ether		C₁₄H₂₂O	详情	详情
(XII)	39586	2,4,4-trimethyl-3-[(E)-3-oxo-1-butenyl]-2-cyclohexen-1-yl acetate		C₁₅H₂₂O₃	详情	详情
(XIII)	39587	3-[(1E)-3-hydroxy-3-methyl-1,4-pentadienyl]-2,4,4-trimethyl-2-cyclohexen-1-ol		C₁₅H₂₄O₂	详情	详情
(XIV)	39588	3-[(1E)-3-hydroxy-3-methyl-1,4-pentadienyl]-2,4,4-trimethyl-2-cyclohexen-1-one		C₁₅H₂₂O₂	详情	详情
(C)	39589	triphenylphosphonium bromide	6399-81-1	C₁₈H₁₆BrP	详情	详情

Extended Information