2',4'-difluoro[1,1'-biphenyl]-4-ol -Drug Synthesis Database

【结构式】

【分子编号】14631

【品名】2',4'-difluoro[1,1'-biphenyl]-4-ol

【CA登记号】

【分子式】C₁₂H₈F₂O

【分子量】206.1917264

【元素组成】C 69.9% H 3.91% F 18.43% O 7.76%

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：(III)

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).

参考文献中间体

合成目标

【1】 Ruyle, W.V.; et al. (Merck & Co., Inc.); Phenyl benzoic acid compounds in compositions and methods for treating inflammation. US 3674870 .
【2】 Howard, J.; et al. (Merck & Co., Inc.); Chemical products. DE 2532559; FR 2288729; GB 1496231; GB 1496232; JP 51034135 .
【3】 Houser, R.W.; Jones, H. (Merck & Co., Inc.); Process for preparing 4-(2,4-difluorophenyl)-salicyclic acid. US 4225730 .
【4】 Ruyle, W.V.; et al. (Merck & Co., Inc.); Halo-substituted 5-phenylbenzoic acids and their derivatives. GB 1175212 .
【5】 Arrigoni-Martelli, E.; Castaner, J.; Diflunisal. Drugs Fut 1978, 3, 4, 28.

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)	23767	Methoxybenzene; Methyl phenyl ether; Anisole	100-66-3	C₇H₈O	详情	详情
(B)	32169	3-Methyl-1-nitrobutane; Isoamyl nitrite	543-87-3	C₅H₁₁NO₂	详情	详情
(I)	19462	2,4-difluoroaniline; 2,4-difluorophenylamine；2,4-Difluoro-benzenamine;1-Amino-2,4-difluorobenzene	367-25-9	C₆H₅F₂N	详情	详情
(II)	33464	2',4'-difluoro[1,1'-biphenyl]-4-yl methyl ether; 2,4-difluoro-4'-methoxy-1,1'-biphenyl		C₁₃H₁₀F₂O	详情	详情
(III)	14631	2',4'-difluoro[1,1'-biphenyl]-4-ol		C₁₂H₈F₂O	详情	详情
(IV)	33465	2,4-difluoro-1,1'-biphenyl		C₁₂H₈F₂	详情	详情
(V)	33466	1-(2',4'-difluoro[1,1'-biphenyl]-4-yl)-1-ethanone		C₁₄H₁₀F₂O	详情	详情
(VI)	33467	2',4'-difluoro[1,1'-biphenyl]-4-yl acetate		C₁₄H₁₀F₂O₂	详情	详情

合成路线2

该中间体在本合成路线中的序号：(I)

Flubichin (V) is prepared by a reaction of 4(3H)-quinazolinone (IV) with 2',4'-difluoro-4-(2-chloroethoxy)biphenyl (III). Compound (III) can be prepared by reaction of 2',4'-difluoro-4-hydroxybiphenyl (I) with 2-chloroethyl p-toluene sulfonate (II). Methanesulfonate of flubichin is obtained by reaction of flubichin base (V) with methanesulfonic acid in chloroform.

参考文献中间体

合成目标

【1】 Fisnerová, L.; Brunová, B.; Maturová, E.; Grimová, J. (SPOFA - United Pharmaceutical Works); Ether deriv. of 4-[3H]-quinazoline, a process for the preparation thereof, and pharmaceutical compsns. AU 8942880; EP 0367944; JP 1990172977 .
【2】 Rejholec, V.; Flubichin Methanesulfonate. Drugs Fut 1991, 16, 8, 715.

中间体序号	中间体编号	品名	CAS号	分子式	供应商	用于合成
(I)	14631	2',4'-difluoro[1,1'-biphenyl]-4-ol		C₁₂H₈F₂O	详情	详情
(II)	14632	2-chloroethyl 4-methylbenzenesulfonate; 2-Chloroethyl-p-toluenesulfonate	80-41-1	C₉H₁₁ClO₃S	详情	详情
(III)	14633	2-chloroethyl 2',4'-difluoro[1,1'-biphenyl]-4-yl ether; 4-(2-chloroethoxy)-2',4'-difluoro-1,1'-biphenyl		C₁₄H₁₁ClF₂O	详情	详情
(IV)	14634	4(3H)-quinazolinone		C₈H₆N₂O	详情	详情
(V)	14635	3-[2-[(2',4'-difluoro[1,1'-biphenyl]-4-yl)oxy]ethyl]-4(3H)-quinazolinone		C₂₂H₁₆F₂N₂O₂	详情	详情

Extended Information