(5E)-3-butyl-6-iodo-1,5-hexadien-3-ol -Drug Synthesis Database

【结构式】

【分子编号】29317

【品名】(5E)-3-butyl-6-iodo-1,5-hexadien-3-ol

【CA登记号】

【分子式】C₁₀H₁₇IO

【分子量】280.14885

【元素组成】C 42.87% H 6.12% I 45.3% O 5.71%

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：(VI)

The reaction of 4-hydroxy-1-octyne (I), with chlorotrimethylsilane and imidazole in DMF gives 4-trimethylsilyloxy-1-octyne (II), which is converted into 1-iodo-4-trimethylsilyloxy-trans-1-octene (III) by reaction with bis(3-methyl-2-butyl)borane (A), trimethylamine oxide, NaOH and finally I2. The hydrolysis of (III) with acetic acid in THF affords 1-iodo-4-hydroxy-trans-1-octene (IV), which is oxidized with pyridinium chlorochromate in methylene chloride yielding 1-iodo-4-oxo-trans-1-octene (V). The Grignard reaction of (V) with vinylmagnesium bromide (B) in THF gives 4-hydroxy-4-vinyl-1-iodo-trans-1-octene (VI), which is protected with trimethylsilyl chloride as before yielding 4-trimethylsilyloxy-4-vinyl-1-iodo-trans-1-octene (VII). The reaction of (VII) with tert-butyllithium in ether and then with copper (1)-1-pentyne-tributylphosphine (C) in HMPT affords the copper salt (VIII), which is condensed with 2-(6-trimethylsilyloxycarbonyl-2-cis-hexenyl)-4-trimethylsilyloxycyclopent-2-en-1-one (IX) in ether - THF giving trimethylsilyl-9-oxo-11alpha,16-bistrimethylsilyloxy-16-vinyl-5-cis-13-trans-prostadienoate (X). The hydrolysis of (X) with acetic acid in THF-water yields 9-oxo-11alpha,16-dihydroxy-16-vinyl-5-cis-13-trans-prostadienoic acid (XI), which is finally methylated with diazomethane in ether.

参考文献中间体

合成目标

【1】 Middlenton, B.F.; Martin, J.W.; Grudzinskas, C.V.; Chen, S.L. (American Cyanamid Co.); Novel prostaglandin compounds. ES 475787; FR 2410648; GB 2009173; US 4198521 .
【2】 Hillier, K.; Blancafort, P.; Serradell, M.N.; Castaner, J.; CL-115,347. Drugs Fut 1983, 8, 4, 307.

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)	20452	bis(1,2-dimethylpropyl)borane	132509-17-2	C₁₀H₂₃B	详情	详情
(I)	29312	1-octyn-4-ol		C₈H₁₄O	详情	详情
(II)	36018	[(1-butyl-3-butynyl)oxy](trimethyl)silane; 1-butyl-3-butynyl trimethylsilyl ether		C₁₁H₂₂OSi	详情	详情
(III)	36019	(E)-1-butyl-4-iodo-3-butenyl trimethylsilyl ether; [[(E)-1-butyl-4-iodo-3-butenyl]oxy](trimethyl)silane		C₁₁H₂₃IOSi	详情	详情
(IV)	29315	(E)-1-iodo-1-octen-4-ol		C₈H₁₅IO	详情	详情
(V)	29316	(E)-1-iodo-1-octen-4-one		C₈H₁₃IO	详情	详情
(VI)	29317	(5E)-3-butyl-6-iodo-1,5-hexadien-3-ol		C₁₀H₁₇IO	详情	详情
(VII)	36020	(E)-1-butyl-4-iodo-1-vinyl-3-butenyl trimethylsilyl ether; [[(E)-1-butyl-4-iodo-1-vinyl-3-butenyl]oxy](trimethyl)silane		C₁₃H₂₅IOSi	详情	详情
(VIII)	36021	[(1E)-4-butyl-4-[(trimethylsilyl)oxy]-1,5-hexadienyl](1-pentynyl)copper		C₁₈H₃₂CuOSi	详情	详情
(IX)	36022	trimethylsilyl (Z)-7-[(3R)-5-oxo-3-[(trimethylsilyl)oxy]-1-cyclopenten-1-yl]-5-heptenoate		C₁₈H₃₂O₄Si₂	详情	详情
(X)	36023	trimethylsilyl (Z)-7-[(1R,2R,3R)-2-[(1E)-4-butyl-4-[(trimethylsilyl)oxy]-1,5-hexadienyl]-5-oxo-3-[(trimethylsilyl)oxy]cyclopentyl]-5-heptenoate		C₃₁H₅₈O₅Si₃	详情	详情
(XI)	36024	(Z)-7-[(1R,2R,3R)-2-[(1E)-4-butyl-4-hydroxy-1,5-hexadienyl]-3-hydroxy-5-oxocyclopentyl]-5-heptenoic acid		C₂₂H₃₄O₅	详情	详情
(C)	29069	1-pentynylcopper		C₅H₇Cu	详情	详情

合成路线2

该中间体在本合成路线中的序号：(VI)

The reaction of 4-hydroxy-1-octyne (I) with chlorotrimethylsilane and imidazole in DMF gives 4-trimethylsilyloxy-1-octyne (II), which is converted to 1-iodo-4-trimethylsilyloxy-trans-1-octene (III) by reaction with bis(3-methyl-2-butyl)borane, trimethylamine oxide, NaOH and finally I2. The hydrolysis of (III) with acetic acid in THF affords 1-iodo-4-hydroxy-trans-1-octene (IV), which is oxidized with pyridinium chlorochromate in methylene chloride yielding 1-iodo-4-oxo-trans-1-octene (V). The Grignard condensation of (V) with vinylmagnesium bromide in THF gives 4 hydroxy-4-vinyl-1-iodo-trans-1-octene (VI), which is protected with trimethylsilyl chloride as before yielding 4-trimethylsilyloxy-4-vinyl-1-iodo-trans-1-octene (VII). The reaction of (VII) with tert-butyllithium in ether and then with copper(I)-1-pentyne-tributylphosphine in HMPT affords the copper salt (VIII), which is condensed with 2-(6-trimethylsilyloxycarbonyl)-2-cis-hexenyl)-4-trimethylsilyloxycyclopent-2-en-1-one (IX) in ether-THF giving trimethylsilyl-9-oxo-11 alpha,16-bis(trimethylsilyloxy)-16-vinyl-5-cis-13-trans-prostadienoate (X). Finally, this compound is hydrolyzed with acetic acid in THF water.

参考文献中间体

合成目标

【1】 Middlenton, B.F.; Martin, J.W.; Grudzinskas, C.V.; Chen, S.L. (American Cyanamid Co.); Novel prostaglandin compounds. ES 475787; FR 2410648; GB 2009173; US 4198521 .
【2】 Middlenton, B.F.; Martin, J.W.; Grudzinskas, C.V.; Chen, S.L. (American Cyanamid Co.); Nouveaux acides 15-désoxy-16-hydroprotanoïques 16-substitués doués d'activité pharmaceutiques et leur procédé de préparation. DE 2813342; ES 468353; FR 2385696; JP 7939047; US 4131737 .
【3】 Pfenning, J.; et al. (American Cyanamid Co.); 15-Deoxy-16-substituted protanoic acids. DE 2837530; ES 472908; FR 2401899; GB 2006186; JP 54046748; JP 7946748 .
【4】 Adaikan, P.G.; Serradell, M.N.; Castaner, J.; DHV-PGE2. Drugs Fut 1985, 10, 5, 382.

中间体序号	中间体编号	品名	CAS号	分子式	供应商	用于合成
(A)	16524	bromo(vinyl)magnesium	1826-67-1	C₂H₃BrMg	详情	详情
(B)	29319	1-Pentynyl copper salt tri(tert-butyl)phosphine complex		C₁₇H₃₄CuP	详情	详情
(I)	29312	1-octyn-4-ol		C₈H₁₄O	详情	详情
(II)	29313	(2-butyl-4-pentynyl)(trimethyl)silane		C₁₂H₂₄Si	详情	详情
(III)	29314	[(E)-2-butyl-5-iodo-4-pentenyl](trimethyl)silane		C₁₂H₂₅ISi	详情	详情
(IV)	29315	(E)-1-iodo-1-octen-4-ol		C₈H₁₅IO	详情	详情
(V)	29316	(E)-1-iodo-1-octen-4-one		C₈H₁₃IO	详情	详情
(VI)	29317	(5E)-3-butyl-6-iodo-1,5-hexadien-3-ol		C₁₀H₁₇IO	详情	详情
(VII)	29318	[(E)-2-butyl-5-iodo-2-vinyl-4-pentenyl](trimethyl)silane		C₁₄H₂₇ISi	详情	详情
(VIII)	29320	[(1E)-4-butyl-4-[(trimethylsilyl)methyl]-1,5-hexadienyl](1-pentynyl)copper		C₁₉H₃₄CuSi	详情	详情
(IX)	29321	(4R)-2-[(Z)-7-oxo-8-(trimethylsilyl)-2-octenyl]-4-[(trimethylsilyl)methyl]-2-cyclopenten-1-one		C₂₀H₃₆O₂Si₂	详情	详情
(X)	29322	(2R,3R,4R)-3-[(1E)-4-butyl-4-[(trimethylsilyl)methyl]-1,5-hexadienyl]-2-[(Z)-7-oxo-8-(trimethylsilyl)-2-octenyl]-4-[(trimethylsilyl)methyl]cyclopentanone		C₃₄H₆₄O₂Si₃	详情	详情

Extended Information