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【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

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.

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.

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