4-(4-chlorophenyl)-1-(1H-imidazol-1-yl)-2-butanol -Drug Synthesis Database

【结构式】

【分子编号】16486

【品名】4-(4-chlorophenyl)-1-(1H-imidazol-1-yl)-2-butanol

【CA登记号】

【分子式】C₁₃H₁₅ClN₂O

【分子量】250.72768

【元素组成】C 62.28% H 6.03% Cl 14.14% N 11.17% O 6.38%

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)

The chlorohydrin (II) is obtained by the reaction of p-chlorobenzylmagnesium chloride (I) with epichlorohydrin (A) in ether. This is then converted to the crystalline alcohol (III) by reaction with sodium imidazole (B) in DMF. On treatment with thionyl chloride is converted to the corresponding chloro compound (IV). When (IV) is reacted with 2,6-dichloro thiophenol (C) in the presence of anhydrous potassium carbonate in acetone, the free base of butoconazole is formed. Neutralization of the free base (V) with nitric acid gives butoconazole.

参考文献中间体

合成目标

【1】 Walker, K.A.M.; et al.; 1-[4-(4-chlorophenyl)-2-(2,6-dichlorophenylthio)n-butil]-1H-imidazole nitrate, a new patent antifungal agent. J Med Chem 1978, 21, 8, 840.
【2】 Arya, V.P.; Butoconazole nitrate. Drugs Fut 1979, 4, 2, 89.

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)	10146	Epichlorohydrin; 2-(Chloromethyl)oxirane	106-89-8	C₃H₅ClO	详情	详情
(B)	10255	Imidazole; 1H-Imidazole	288-32-4	C₃H₄N₂	详情	详情
(I)	33290	Bromo(4-chlorobenzyl)magnesium; p-Chlorobenzylmagnesium chloride		C₇H₆BrClMg	详情	详情
(II)	33291	1-chloro-4-(4-chlorophenyl)-2-butanol		C₁₀H₁₂Cl₂O	详情	详情
(III)	16486	4-(4-chlorophenyl)-1-(1H-imidazol-1-yl)-2-butanol		C₁₃H₁₅ClN₂O	详情	详情
(IV)	33292	1-[2-chloro-4-(4-chlorophenyl)butyl]-1H-imidazole		C₁₃H₁₄Cl₂N₂	详情	详情
(V)	33294	1-[4-(4-chlorophenyl)-2-[(2,6-dichlorophenyl)sulfanyl]butyl]-1H-imidazole; 3-(4-chlorophenyl)-1-(1H-imidazol-1-ylmethyl)propyl 2,6-dichlorophenyl sulfide		C₁₉H₁₇Cl₃N₂S	详情	详情
(C)	33293	2,6-Dichloro thiophenol; 2,6-Dichlorobenzenethiol; 2,6-Dichlorophenylhydrosulfide	24966-39-0	C₆H₄Cl₂S	详情	详情

合成路线2

该中间体在本合成路线中的序号：(VI)

Reaction of the Grignard reagent derived from 4-chlorobenzyl bromide (I) with allyl bromide (II) gives 4-(4-chlorophenyl)but-1-ene (III), which is epoxidized with peracetic acid in dichloromethane to yield 4-(4-chlorophenyl)-1,2-epoxybutane (IV). Opening of (IV) with the anion of imidazole (V) gives 1-[4-(4-chlorophenyl)-2-hydroxybutyl]imidazole (VI), which is oxidized under Swern conditions to 4-(4-chlorophenyl)-1-(1-imidazolyl)-2-butanone (VII). Ketone (VII) is then reacted with (S)-solketal tosylate [(S)-1,2-O-isopropylideneglycerol-3-O-tosylate] (VIII) in the presence of p-toluenesulfonic acid in toluene to give a mixture of stereoisomers, and (2S,4S)-cis-2-[2-(4-chlorophenyl)ethyl]-2-(imidazol-1-ylmethyl)-4-(p-toluenesulfonyloxy)methyl-1,3-dioxolane (IX) is then separated by crystallization. Finally, (IX) is treated with 4-aminothiophenol (X) in the presence of potassium carbonate in acetone.

参考文献中间体

合成目标

【1】 Dyson, N.H.; Gardner, J.O.; Prince, A.; Kertesz, D.J. (Syntex (USA), Inc.); Process for preparing 1,3-dioxolane derivs. JP 1995508002; US 5208331 .
【2】 Walker, K.A.; Burton, P.M.; Swinney, D.C. (Syntex (USA), Inc.); 1,3-Dioxolane derivs. as cholesterol lowering agents. JP 1992308588; US 5158949 .
【3】 Walker, K.A.M.; Rotstein, D.M.; Kertesz, D.J.; et al.; Selective inhibition of mammalian lanosterol 14alpha-demethylase: A possible strategy for cholesterol lowering. J Med Chem 1993, 36, 15, 2235-7.
【4】 Prous, J.; Mealy, N.; Castañer, J.; RS-21607-197. Drugs Fut 1994, 19, 2, 125.

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)	16481	1-(bromomethyl)-4-chlorobenzene	622-95-7	C₇H₆BrCl	详情	详情
(II)	11463	3-Bromo-1-propene; 3-Bromopropene；allyl bromide	106-95-6	C₃H₅Br	详情	详情
(III)	16483	1-(3-butenyl)-4-chlorobenzene		C₁₀H₁₁Cl	详情	详情
(IV)	16484	2-(4-chlorophenethyl)oxirane		C₁₀H₁₁ClO	详情	详情
(V)	10255	Imidazole; 1H-Imidazole	288-32-4	C₃H₄N₂	详情	详情
(VI)	16486	4-(4-chlorophenyl)-1-(1H-imidazol-1-yl)-2-butanol		C₁₃H₁₅ClN₂O	详情	详情
(VII)	16487	4-(4-chlorophenyl)-1-(1H-imidazol-1-yl)-2-butanone		C₁₃H₁₃ClN₂O	详情	详情
(VIII)	16488	(2S)-2,3-dihydroxypropyl 4-methylbenzenesulfonate		C₁₀H₁₄O₅S	详情	详情
(IX)	16489	[(2S,4S)-2-(4-chlorophenethyl)-2-(1H-imidazol-1-ylmethyl)-1,3-dioxolan-4-yl]methyl 4-methylbenzenesulfonate		C₂₃H₂₅ClN₂O₅S	详情	详情
(X)	16490	4-aminophenylhydrosulfide; 4-aminothiophenol; 4-aminobenzenethiol	1193-02-8	C₆H₇NS	详情	详情

Extended Information