合成路线:Compound can be prepared in two different ways both starting from 2,4-difluoroaniline (I):1) The diazotation of (I) with isoamyl nitrite (B) and condensation with anisole (A) gives 4-(2,4-difluorophenyl)anisole (II),which is hydrolyzed with HI in refluxing acetic acid yielding 4-(2,4-difluorophenyl)phenol (III).Finally,this compound is carbonated with K2CO3 and CO2 at 175 C and 1300 p.s.i.2) The diazotation of (I) with isoamyl nitrite (B) and then condensation with benzene by means of powdered Cu gives 2,4-difluorobiphenyl (IV),which is acetylated with acetic anhydride by means of AlCl3 in CH2Cl2 yielding 4-(2,4-difluorophenyl)acetophenone (V).The oxidation of (V) with H2O2 in refluxing CH2Cl2 affords 4-(2,4-difluorophenyl)phenyl acetate (VI),which can be hydrolyzed with NaOH in refluxing water to give the phenol (III).
参考文献标题:Phenyl benzoic acid compounds in compositions and methods for treating inflammation
文献作者:Ruyle,W.V.; et al.(Merck & Co.,Inc.)
参考来源:US 3674870
合成路线:Compound can be prepared in two different ways both starting from 2,4-difluoroaniline (I):1) The diazotation of (I) with isoamyl nitrite (B) and condensation with anisole (A) gives 4-(2,4-difluorophenyl)anisole (II),which is hydrolyzed with HI in refluxing acetic acid yielding 4-(2,4-difluorophenyl)phenol (III).Finally,this compound is carbonated with K2CO3 and CO2 at 175 C and 1300 p.s.i.2) The diazotation of (I) with isoamyl nitrite (B) and then condensation with benzene by means of powdered Cu gives 2,4-difluorobiphenyl (IV),which is acetylated with acetic anhydride by means of AlCl3 in CH2Cl2 yielding 4-(2,4-difluorophenyl)acetophenone (V).The oxidation of (V) with H2O2 in refluxing CH2Cl2 affords 4-(2,4-difluorophenyl)phenyl acetate (VI),which can be hydrolyzed with NaOH in refluxing water to give the phenol (III).
参考文献标题:Chemical products
文献作者:Howard,J.; et al.(Merck & Co.,Inc.)
参考来源:DE 2532559; FR 2288729; GB 1496231; GB 1496232; JP 51034135
合成路线:Compound can be prepared in two different ways both starting from 2,4-difluoroaniline (I):1) The diazotation of (I) with isoamyl nitrite (B) and condensation with anisole (A) gives 4-(2,4-difluorophenyl)anisole (II),which is hydrolyzed with HI in refluxing acetic acid yielding 4-(2,4-difluorophenyl)phenol (III).Finally,this compound is carbonated with K2CO3 and CO2 at 175 C and 1300 p.s.i.2) The diazotation of (I) with isoamyl nitrite (B) and then condensation with benzene by means of powdered Cu gives 2,4-difluorobiphenyl (IV),which is acetylated with acetic anhydride by means of AlCl3 in CH2Cl2 yielding 4-(2,4-difluorophenyl)acetophenone (V).The oxidation of (V) with H2O2 in refluxing CH2Cl2 affords 4-(2,4-difluorophenyl)phenyl acetate (VI),which can be hydrolyzed with NaOH in refluxing water to give the phenol (III).
参考文献标题:Process for preparing 4-(2,4-difluorophenyl)-salicyclic acid
文献作者:Houser,R.W.; Jones,H.(Merck & Co.,Inc.)
参考来源:US 4225730
合成路线:Compound can be prepared in two different ways both starting from 2,4-difluoroaniline (I):1) The diazotation of (I) with isoamyl nitrite (B) and condensation with anisole (A) gives 4-(2,4-difluorophenyl)anisole (II),which is hydrolyzed with HI in refluxing acetic acid yielding 4-(2,4-difluorophenyl)phenol (III).Finally,this compound is carbonated with K2CO3 and CO2 at 175 C and 1300 p.s.i.2) The diazotation of (I) with isoamyl nitrite (B) and then condensation with benzene by means of powdered Cu gives 2,4-difluorobiphenyl (IV),which is acetylated with acetic anhydride by means of AlCl3 in CH2Cl2 yielding 4-(2,4-difluorophenyl)acetophenone (V).The oxidation of (V) with H2O2 in refluxing CH2Cl2 affords 4-(2,4-difluorophenyl)phenyl acetate (VI),which can be hydrolyzed with NaOH in refluxing water to give the phenol (III).
参考文献标题:Diflunisal
文献作者:Arrigoni-Martelli,E.; Castar,J.
参考来源:Drugs Fut 1978,3(4),28
合成路线:A facile preparation method for diflunisal has been reported: Reaction of 2,4-difluoroiodobenzene (I) with powdered Zn activated with 1,2-dibromoethane in DMF gives the 2,4-difluorophenylzinc iodide (II),which is condensed with 2-acetoxy-5-iodobenzoic acid methyl ester (III) by means of Pd(PPh3)4 in DMF to yield 4-acetoxy-2',4'-difluorobiphenyl-3-carboxylic acid methyl ester (IV).Finally,this compound is deacetylated and hydrolyzed with NaHCO3 in THF/water.
参考文献标题:A facile preparation of fluoroaryl zinc halides: An application to the synthesis of diflunisal
文献作者:Lee,S.J.; Chung,S.; Jeong,N.; Choi,K.H.
参考来源:Bull Korean Chem Soc 2000,21(2),165
产品链接: CAS No. 22494-42-4››