【结 构 式】 |
【分子编号】29315 【品名】(E)-1-iodo-1-octen-4-ol 【CA登记号】 |
【 分 子 式 】C8H15IO 【 分 子 量 】254.11097 【元素组成】C 37.81% H 5.95% I 49.94% O 6.3% |
合成路线1
该中间体在本合成路线中的序号:(IV)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:(IV)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 |