5-(benzyloxy)-5-oxopentanoic acid -Drug Synthesis Database

【结构式】

【分子编号】19943

【品名】5-(benzyloxy)-5-oxopentanoic acid

【CA登记号】

【分子式】C₁₂H₁₄O₄

【分子量】222.24076

【元素组成】C 64.85% H 6.35% O 28.8%

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：(IV)

The condensation of m-methoxybenzaldehyde (I) with cyclohexanone (II) by means of KOH in refluxing water gives m-methoxybenzalcyclohexanone (III), which by reaction first with dimethylamine (A) in ether and then reduction with LiAlH4 in the same solvent affords cis-2-(alpha-dimethylamino-m-methoxybenzyl)cyclohexanol (IV). The hydrolysis of (IV) with HCl in isopropanol yields the racemic product, which is finally resolved into the corresponding optical isomers with tartaric acid.

参考文献中间体

合成目标

【1】 Yardley, J.P.; Russell, P.B.; US 3928626 .
【2】 Paton, D.M.; Castaner, J.; Ciramadol. Drugs Fut 1980, 5, 6, 283.

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)	20589	3-methoxybenzaldehyde; m-Anisaldehyde	591-31-1	C₈H₈O₂	详情	详情
(II)	11059	Cyclohexanone	108-94-1	C₆H₁₀O	详情	详情
(III)	39125	2-[(E)-(3-methoxyphenyl)methylidene]cyclohexanone		C₁₄H₁₆O₂	详情	详情
(IV)	19943	5-(benzyloxy)-5-oxopentanoic acid		C₁₂H₁₄O₄	详情	详情
(V)	39126	(1R,2R)-2-[(R)-(dimethylamino)(3-methoxyphenyl)methyl]cyclohexanol		C₁₆H₂₅NO₂	详情	详情

合成路线2

该中间体在本合成路线中的序号：(VIa)

Treatment of 6-methoxy-1,4-dimethylcarbazole (I) with pivaloyl chloride and NaI in refluxing acetonitrile cleaved the methyl ether and afforded pivalate (II). The condensation of this with the Vilsmeier reagent from N-methylformanilide and phosphoryl chloride gave the formyl compound (III). Condensation of (III) with aminoacetaldehyde diethyl acetal in the presence of a catalytic amount of p-toluenesulfonic acid in refluxing toluene with azeotropic distillation of water, followed by hydrogenation of the intermediate imine in the presence of PtO2, afforded the corresponding amine, which was subsequently converted to the N-tosyl derivative (IV) on treatment with tosyl chloride and triethylamine. Refluxing (IV) with hydrogen chloride in aqueous dioxane effected cyclization, with simultaneous elimination of the tosyl and pivaloyl groups yielding the 9-hydroxyellipticine (V) (1). Glutaric acid monobenzyl ester (VIa) was converted to the active ester (VII) on treatment with 1-hydroxybenzotriazole (VIb) and dicyclohexyl carbodiimide, and this was condensed with (V) to afford diester (VIII). Finally, the benzyl ester was deprotected by hydrogenolysis in the presence of palladium-carbon and hydrogen.

参考文献中间体

合成目标

【1】 Harada, N.; et al.; Synthesis and antitumor activity of 9-acyloxyellipticines. Chem Pharm Bull 1997, 45, 7, 1156.
【2】 Tsujihara, K.; Harada, N.; Ozaki, K.; Ohashi, M.; Oda, K. (Tanabe Seiyaku Co., Ltd.); Ellipticine derivs. with antitumor activity. EP 0608876; JP 1994279441; US 5605904 .

中间体序号	中间体编号	品名	CAS号	分子式	供应商	用于合成
(VIb)	10184	1H-1,2,3-Benzotriazol-1-ol; 1-Hydroxybenzotriazole; 1H-Benzotriazol-1-ol; 1-Benzotriazolol	2592-95-2	C₆H₅N₃O	详情	详情
(VIa)	19943	5-(benzyloxy)-5-oxopentanoic acid		C₁₂H₁₄O₄	详情	详情
(I)	19938	5,8-dimethyl-9H-carbazol-3-yl methyl ether; 6-methoxy-1,4-dimethyl-9H-carbazole		C₁₅H₁₅NO	详情	详情
(II)	19939	5,8-dimethyl-9H-carbazol-3-yl pivalate		C₁₉H₂₁NO₂	详情	详情
(III)	19940	6-formyl-5,8-dimethyl-9H-carbazol-3-yl pivalate		C₂₀H₂₁NO₃	详情	详情
(IV)	19941	6-([(2,2-diethoxyethyl)[(4-methylphenyl)sulfonyl]amino]methyl)-5,8-dimethyl-9H-carbazol-3-yl pivalate		C₃₃H₄₂N₂O₆S	详情	详情
(V)	19942	5,11-dimethyl-6H-pyrido[4,3-b]carbazol-9-ol hydrochloride		C₁₇H₁₅ClN₂O	详情	详情
(VII)	19944	benzyl 5-(1H-1,2,3-benzotriazol-1-yloxy)-5-oxopentanoate		C₁₈H₁₇N₃O₄	详情	详情
(VIII)	19945	1-benzyl 5-(5,11-dimethyl-6H-pyrido[4,3-b]carbazol-9-yl) pentanedioate		C₂₉H₂₆N₂O₄	详情	详情

Extended Information