4-(3,4-dichlorophenyl)-4-phenylbutanoyl chloride -Drug Synthesis Database

【结构式】

【分子编号】30582

【品名】4-(3,4-dichlorophenyl)-4-phenylbutanoyl chloride

【CA登记号】

【分子式】C₁₆H₁₃Cl₃O

【分子量】327.63672

【元素组成】C 58.66% H 4% Cl 32.46% O 4.88%

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：(VIII)

The Friedel-Kraft's reaction of benzene (I) and 3,4-dichlorobenzoyl chloride (II) by means of AlCl3 in dichloromethane gives 3,4-dichlorobenzophenone (III), which is condensed with diethyl succinate (IV) by means of potassium tert-butoxide in tert-butyl alcohol yielding ethyl 3-ethoxycarbonyl-4-(3,4-dichlorophenyl)-4-phenylbut-3-enoate (V). Hydrolysis of (V) with HBr in refluxing acetic acid affords 4-(3,4-dichlorophenyl)-4-phenylbut-3-enoic acid (VI), which is hydrogenated with H2 over Pd/C in ethyl acetate giving 4-(3,4-dichlorophenyl)-4-phenylbutanoic acid (VII), which is converted into the corresponding acyl chloride (VIII) with refluxing SOCl2. Cyclization of (VIII) with AlCl3 in CS2 yields 4-(3,4-dichlorophenyl)-3,4-dihydro-1-(2H)-naphthalenone (IX), which is treated with methylamine and TiCl4 in THF affording the corresponding Schiff base (X). Finally, this compound is reduced with H2 over Pd/C in THF.

参考文献中间体

合成目标

【1】 Kraska, A.R.; Welch, W.M. Jr.; Koe, B.K.; Harbert, C.A. (Pfizer Inc.); Antidepressant derivatives of cis-4-phenyl-1,2,3,4-tetrahydro-1-naphtalenamine. EP 0030081; JP 1981086137; US 4536518 .
【2】 Castaner, J.; Serradell, M.N.; Sertraline. Drugs Fut 1984, 9, 4, 277.

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)	13364	Benzene	71-43-2	C₆H₆	详情	详情
(II)	26356	3,4-dichlorobenzoyl chloride	3024-72-4	C₇H₃Cl₃O	详情	详情
(III)	30578	(3,4-dichlorophenyl)(phenyl)methanone	6284-79-3	C₁₃H₈Cl₂O	详情	详情
(IV)	12313	diethyl succinate	123-25-1	C₈H₁₄O₄	详情	详情
(V)	30579	diethyl 2-[(Z)-(3,4-dichlorophenyl)(phenyl)methylidene]succinate		C₂₁H₂₀Cl₂O₄	详情	详情
(VI)	30580	(E)-4-(3,4-dichlorophenyl)-4-phenyl-3-butenoic acid		C₁₆H₁₂Cl₂O₂	详情	详情
(VII)	30581	4-(3,4-dichlorophenyl)-4-phenylbutyric acid		C₁₆H₁₄Cl₂O₂	详情	详情
(VIII)	30582	4-(3,4-dichlorophenyl)-4-phenylbutanoyl chloride		C₁₆H₁₃Cl₃O	详情	详情
(IX)	30583	4-(3,4-dichlorophenyl)-3,4-dihydro-1(2H)-naphthalenone; 4-(3',4'-Dichlorophenyl)-1-tetralone	79580-19-3	C₁₆H₁₂Cl₂O	详情	详情
(X)	30584	N-[4-(3,4-dichlorophenyl)-3,4-dihydro-1(2H)-naphthalenylidene]-N-methylamine; N-[4-(3,4-dichlorophenyl)-3,4-dihydro-1(2H)-naphthalenylidene]methanamine		C₁₇H₁₅Cl₂N	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 reaction of intermediate 4-(3,4-dichlorophenyl)-4-phenylbutyric acid (I) (see scheme number 09017202a intermediate (VII)) with (COCl)2 in dichloromethane gives the acyl chloride (II), which is condensed with methyl carbamate (III) in hot toluene to yield N-[4-(3,4-dichlorophenyl)-4-phenylbutyryl]carbamic acid methyl ester (IV). The reduction of (IV) with DIBAL in toluene/dichloromethane affords the hydroxybutyl derivative (V), which is cyclized by means of TiCl4 in dichloromethane to provide N-[4-(3,4-dichlorophenyl)-1,2,3,4-tetrahydro-1-naphthyl]carbamic acid methyl ester as a mixture of the cis and trans isomers, easily separated by chromatography. Finally, the desired cis isomer (VI) is reduced with LiAlH4 in THF to afford the target (rac)-sertraline.

参考文献中间体

合成目标

【1】 DeNinno, M.P.; et al.; The preparation and intra- and intermolecular addition reactions of acyclic N-acylimines: Applications to the synthesis of (±)-sertraline. J Org Chem 2001, 66, 21, 6988.

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)	30581	4-(3,4-dichlorophenyl)-4-phenylbutyric acid		C₁₆H₁₄Cl₂O₂	详情	详情
(II)	30582	4-(3,4-dichlorophenyl)-4-phenylbutanoyl chloride		C₁₆H₁₃Cl₃O	详情	详情
(III)	40724	methyl carbamate; carbamic acid methyl ester	598-55-0	C₂H₅NO₂	详情	详情
(IV)	58595	methyl 4-(3,4-dichlorophenyl)-4-phenylbutanoylcarbamate		C₁₈H₁₇Cl₂NO₃	详情	详情
(V)	58596	methyl 4-(3,4-dichlorophenyl)-1-hydroxy-4-phenylbutylcarbamate		C₁₈H₁₉Cl₂NO₃	详情	详情
(VI)	34049	methyl (1S,4S)-4-(3,4-dichlorophenyl)-1,2,3,4-tetrahydro-1-naphthalenylcarbamate		C₁₈H₁₇Cl₂NO₂	详情	详情

Extended Information