2,4,5-trichloro-10,11-dihydro-5H-dibenzo[a,d]cycloheptene -Drug Synthesis Database

【结构式】

【分子编号】14364

【品名】2,4,5-trichloro-10,11-dihydro-5H-dibenzo[a,d]cycloheptene

【CA登记号】

【分子式】C₁₅H₁₁Cl₃

【分子量】297.61044

【元素组成】C 60.54% H 3.73% Cl 35.74%

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 reduction of 2,4-dichloro-10,11-dihydro-5H-dibenzo[a,d]cyclohepten-5-one (I) with NaBH4 in methanol gives the corresponding alcohol (II), which is treated with refluxing SOCl2 to yield 2,4,5-trichloro-10,11-dihydro-5H-dibenzo[a,d]cycloheptene (III). Finally, this compound is condensed with imidazole (IV) in refluxing DMF and salified with nitric acid in isopropanol/diisopropyl ether.

参考文献中间体

合成目标

【1】 Rabasseda, X.; Castaner, J.; Font, E.; Eberconazole Nitrate. Drugs Fut 1996, 21, 8, 792.
【2】 Andreoli Rovati, R.; Cepero Mestres, R. (Sociedad Espanola de Especialidades Farmaco-Terapeuticas SA); Dichlorosubstd. imidazole derivs. as antifungal agents. AU 9052554; EP 0392326; US 5177099 .

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)	14362	2,4-dichloro-10,11-dihydro-5H-dibenzo[a,d]cyclohepten-5-one		C₁₅H₁₀Cl₂O	详情	详情
(II)	14363	2,4-dichloro-10,11-dihydro-5H-dibenzo[a,d]cyclohepten-5-ol		C₁₅H₁₂Cl₂O	详情	详情
(III)	14364	2,4,5-trichloro-10,11-dihydro-5H-dibenzo[a,d]cycloheptene		C₁₅H₁₁Cl₃	详情	详情
(IV)	10255	Imidazole; 1H-Imidazole	288-32-4	C₃H₄N₂	详情	详情

合成路线2

该中间体在本合成路线中的序号：(VIII)

A process useful for the industrial preparation of eberconazole has been reported: The Wittig condensation of 2-(methoxycarbonyl)benzyl(triphenyl)phosphonium bromide (I) with 3,5-dichlorobenzaldehyde (II) by means of NaH in DMF gives 2-[2-(3,5-dichlorophenyl)vinyl]benzoic acid methyl ester (III), which is hydrolyzed with NaOH in methanol to the corresponding free acid (IV). The hydrogenation of (IV) with H2 over Pd/C in methanol affords 2-[2-(3,5-dichlorophenyl)ethyl]benzoic acid (V), which is cyclized to 2,4-dichloro-10,11-dihydro-5H-dibenzo[a,d]cyclohepten-5-one (VI) by means of polyphosphoric acid. The reduction of (VI) with NaBH4 yields the corresponding carbinol (VII), which is treated with SOCl2 affording the chloride (VIII). Finally, this compound is condensed with imidazole (IX) in refluxing DMF.

参考文献中间体

合成目标

【1】 Farrerons Gallemi, C.; Monserrat Vidal, C.; Miquel Bono, I.J. (Laboratorios Salvat SA); Process for the preparation of eberconazol and intermediates thereof. WO 9921838 .

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)	26013	[2-(methoxycarbonyl)benzyl](triphenyl)phosphonium bromide		C₂₇H₂₄BrO₂P	详情	详情
(II)	24169	3,5-dichlorobenzaldehyde	10203-08-4	C₇H₄Cl₂O	详情	详情
(III)	26014	methyl 2-[(E)-2-(3,5-dichlorophenyl)ethenyl]benzoate		C₁₆H₁₂Cl₂O₂	详情	详情
(IV)	26015	2-[(E)-2-(3,5-dichlorophenyl)ethenyl]benzoic acid		C₁₅H₁₀Cl₂O₂	详情	详情
(V)	26016	2-(3,5-dichlorophenethyl)benzoic acid		C₁₅H₁₂Cl₂O₂	详情	详情
(VI)	14362	2,4-dichloro-10,11-dihydro-5H-dibenzo[a,d]cyclohepten-5-one		C₁₅H₁₀Cl₂O	详情	详情
(VII)	14363	2,4-dichloro-10,11-dihydro-5H-dibenzo[a,d]cyclohepten-5-ol		C₁₅H₁₂Cl₂O	详情	详情
(VIII)	14364	2,4,5-trichloro-10,11-dihydro-5H-dibenzo[a,d]cycloheptene		C₁₅H₁₁Cl₃	详情	详情
(IX)	10255	Imidazole; 1H-Imidazole	288-32-4	C₃H₄N₂	详情	详情

Extended Information