【结 构 式】 |
【分子编号】41476 【品名】1-fluoro-4-[4-(4-vinylphenoxy)butyl]benzene; 4-(4-fluorophenyl)butyl 4-vinylphenyl ether 【CA登记号】 |
【 分 子 式 】C18H19FO 【 分 子 量 】270.3466632 【元素组成】C 79.97% H 7.08% F 7.03% O 5.92% |
合成路线1
该中间体在本合成路线中的序号:(V)Reduction of 3-(4-fluorobenzoyl)propionic acid (I) by means of AlCl3 in CH2Cl2 and borane/tert-butylamine complex yields alcohol (II), which is then converted into aldehyde (IV) by reaction with 4-hydroxybenzaldehyde (III) in presence of PPh3 in THF and diethyl azodicarboxylate. Treatment of (IV) with a solution of methyltriphenylphosphonium bromide in THF and a solution of n-BuLi in hexane affords styrene derivative (V), which couples with 2’-hydroxy-3’-iodoacetophenone (VI) in presence of Et3N and Pd(OAc)2 in CH3CN to provide (VII). Cyclization of (VII) by means of a first treatment with NaOEt in EtOH followed by reaction with diethyl oxalate in Et2O/EtOH yields benzopyrane derivative (VIII) which is then hydrolyzed with NaOH in THF/MeOH to give (IX). Carboxylic acid (IX) is first converted into carboxamide (X) by treatment with a saturated NH3 solution in MeOH and then into carbonitrile (XI) by means of POCl3 in DMF. Finally, treatment of (XI) with a solution of NaN3, NH4Cl and DMF leads to the formation of the desired product.
【1】 Carganico, G.; Mauleon Casellas, D.; Pascual Avellana, J.; Garcia Perez, M.L.; Palomer Benet, A. (Menarini Industrie Farma Riunite srl); Benzopyran derivs. having leukotriene-antagonistic action. EP 0888327; ES 2127106; JP 2000506878; US 5990142; WO 9734885 . |
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) | 17571 | Diethyl oxalate; Ethyl 2-ethoxy-2-oxoacetate | 95-92-1 | C6H10O4 | 详情 | 详情 |
(A) | 30484 | Methyl(triphenyl)phosphonium bromide | 1779-49-3 | C19H18BrP | 详情 | 详情 |
(I) | 39863 | 4-(4-fluorophenyl)-4-oxobutyric acid | 366-77-8 | C10H9FO3 | 详情 | 详情 |
(II) | 41474 | 4-(4-fluorophenyl)-1-butanol | C10H13FO | 详情 | 详情 | |
(III) | 13433 | 4-Hydroxybenzaldehyde; p-Hydroxybenzaldehyde | 123-08-0 | C7H6O2 | 详情 | 详情 |
(IV) | 41475 | 4-[4-(4-fluorophenyl)butoxy]benzaldehyde | C17H17FO2 | 详情 | 详情 | |
(V) | 41476 | 1-fluoro-4-[4-(4-vinylphenoxy)butyl]benzene; 4-(4-fluorophenyl)butyl 4-vinylphenyl ether | C18H19FO | 详情 | 详情 | |
(VI) | 27290 | 1-(2-hydroxy-3-iodophenyl)-1-ethanone | C8H7IO2 | 详情 | 详情 | |
(VII) | 41477 | 1-[3-((E)-2-[4-[4-(4-fluorophenyl)butoxy]phenyl]ethenyl)-2-hydroxyphenyl]-1-ethanone | C26H25FO3 | 详情 | 详情 | |
(VIII) | 41478 | ethyl 8-((E)-2-[4-[4-(4-fluorophenyl)butoxy]phenyl]ethenyl)-4-oxo-4H-chromene-2-carboxylate | C30H27FO5 | 详情 | 详情 | |
(IX) | 41479 | 8-((E)-2-[4-[4-(4-fluorophenyl)butoxy]phenyl]ethenyl)-4-oxo-4H-chromene-2-carboxylic acid | C28H23FO5 | 详情 | 详情 | |
(X) | 41480 | 8-((E)-2-[4-[4-(4-fluorophenyl)butoxy]phenyl]ethenyl)-4-oxo-4H-chromene-2-carboxamide | C28H24FNO4 | 详情 | 详情 | |
(XI) | 41481 | 8-((E)-2-[4-[4-(4-fluorophenyl)butoxy]phenyl]ethenyl)-4-oxo-4H-chromene-2-carbonitrile | C28H22FNO3 | 详情 | 详情 |