methyl 2-(3,4-dichlorophenyl)acetate -Drug Synthesis Database

【结构式】

【分子编号】47947

【品名】methyl 2-(3,4-dichlorophenyl)acetate

【CA登记号】

【分子式】C₉H₈Cl₂O₂

【分子量】219.06672

【元素组成】C 49.35% H 3.68% Cl 32.37% O 14.61%

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：(V)

Reaction of 2-chloropyrazine (I) with 3,4-dichlorophenylmagnesium bromide (II) in the presence of [1,2-bis(diphenylphosphino)ethane]nickel(II) chloride produced the 2-arylpyrazine (III), which was reduced to the corresponding piperazine (IV) by means of DIBAL in THF. In a different procedure, bromination of methyl 3,4-dichlorophenylacetate (V) using N-bromosuccinimide, followed by reaction of the resulting bromo ester (VI) with ethylenediamine (VII) afforded the piperazinone (VIII), which was further reduced to (IV) by using LiAlH4 in Et2O.

参考文献中间体

合成目标

【1】 Anthes, J.C.; McPhail, A.T.; Blythin, D.J.; Shue, H.-J.; Chen, X.; Piwinski, J.J.; shih, N.-Y.; Discovery of Sch 62373 and analogs, of novel series of 2-phenylpiperazines exhibiting potent dual NK1/NK2 antagonist activity. 221st ACS Natl Meet (April 1 2001, San Diego) 2001, Abst MEDI 244.
【2】 Shue, H.-J.; Shih, N.-Y.; Blythin, D.J.; Chen, X.; Tom, W.C.; Piwinski, J.J.; McCormick, K.D. (Schering Corp.); Piperazino derivs. as neurokinin antagonists. EP 0823906; US 5719156; WO 9634864 .
【3】 Piwinski, J.J.; McCormick, K.D.; Shue, H.-J.; Chen, X.; Shih, N.-Y.; Blythin, D.J. (Schering Corp.); Piperazino derivs. as neurokinin antagonists. EP 0850236; JP 2000344766; US 5795894; US 5892039; WO 9708166 .

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)	24075	2-chloropyrazine	14508-49-7	C₄H₃ClN₂	详情	详情
(II)	10069	Bromo(3,4-dichlorophenyl)magnesium	79175-35-2	C₆H₃BrCl₂Mg	详情	详情
(III)	47945	2-(3,4-dichlorophenyl)pyrazine		C₁₀H₆Cl₂N₂	详情	详情
(IV)	47946	2-(3,4-dichlorophenyl)piperazine		C₁₀H₁₂Cl₂N₂	详情	详情
(V)	47947	methyl 2-(3,4-dichlorophenyl)acetate		C₉H₈Cl₂O₂	详情	详情
(VI)	47948	methyl 2-bromo-2-(3,4-dichlorophenyl)acetate		C₉H₇BrCl₂O₂	详情	详情
(VII)	14754	ethylenediamine;1,2-Diaminoethane;ethane-1,2-diamine；1,2-Ethanediamine	107-15-3	C₂H₈N₂	详情	详情
(VIII)	47949	3-(3,4-dichlorophenyl)-2-piperazinone		C₁₀H₁₀Cl₂N₂O	详情	详情

合成路线2

该中间体在本合成路线中的序号：(II)

The esterification of 3,4-dichlorophenylacetic acid (I) with methanol and ClH gives the methyl ester (II), which is alkylated with allyl bromide and LDA in THF to yield 2-(3,4-dichlorophenyl)-4-pentenoic acid methyl ester (IV). The hydrolysis of (IV) with LiOH in MeOH/water affords the corresponding free acid (V), which is epoxidated with MCPBA in refluxing chloroform to provide epoxide (VI), which, without isolation, is treated in acid medium, giving the tetrahydrofuranone (VII). The silylation of the OH group of (VII) with Tbdms-Cl and imidazole in DMF yields the protected silyl ether (VIII), which is treated with LDA in THF to afford the lithium enolate (IX). The reaction of (IX) with phenylselenyl chloride in THF provides the phenylselenyl derivative (X), which is oxidized with MCPBA to the corresponding selenoxide. This nonisolated compound undergoes spontaneous syn elimination to give, after hydrolysis of the silyl ether with AcOH, 3-(3,4-dichlorophenyl)-5-(hydroxymethyl)furan-2(5H)-one (XI). Finally, this compound is esterified with pivaloyl chloride and pyridine in dichloromethane to afford the target ester.

参考文献中间体

合成目标

【1】 Pour, M.; et al.; 3-Phenyl-5-acyloxymethyl-2H,5H-furan-2-ones: Synthesis and biological activity of a novel group of potential antifungal drugs. J Med Chem 2001, 44, 17, 2701.

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)	30414	2-(3,4-dichlorophenyl)acetic acid；2-(3,4-Dichlorophenyl)acetic acid	5807-30-7	C₈H₆Cl₂O₂	详情	详情
(II)	47947	methyl 2-(3,4-dichlorophenyl)acetate		C₉H₈Cl₂O₂	详情	详情
(III)	11463	3-Bromo-1-propene; 3-Bromopropene；allyl bromide	106-95-6	C₃H₅Br	详情	详情
(IV)	50420	methyl 2-(3,4-dichlorophenyl)-4-pentenoate		C₁₂H₁₂Cl₂O₂	详情	详情
(V)	50421	2-(3,4-dichlorophenyl)-4-pentenoic acid		C₁₁H₁₀Cl₂O₂	详情	详情
(VI)	50422	2-(3,4-dichlorophenyl)-3-(2-oxiranyl)propionic acid		C₁₁H₁₀Cl₂O₃	详情	详情
(VII)	50423	3-(3,4-dichlorophenyl)-5-(hydroxymethyl)dihydro-2(3H)-furanone		C₁₁H₁₀Cl₂O₃	详情	详情
(VIII)	50424	5-([[tert-butyl(dimethyl)silyl]oxy]methyl)-3-(3,4-dichlorophenyl)dihydro-2(3H)-furanone		C₁₇H₂₄Cl₂O₃Si	详情	详情
(IX)	50425			C₁₇H₂₃Cl₂LiO₃Si	详情	详情
(X)	50426	5-([[tert-butyl(dimethyl)silyl]oxy]methyl)-3-(3,4-dichlorophenyl)-3-(phenylselanyl)dihydro-2(3H)-furanone		C₂₃H₂₈Cl₂O₃SeSi	详情	详情
(XI)	50427	3-(3,4-dichlorophenyl)-5-(hydroxymethyl)-2(5H)-furanone		C₁₁H₈Cl₂O₃	详情	详情
(XII)	44281	pivalic acid	75-98-9	C₅H₁₀O₂	详情	详情

Extended Information