ethyl 2-(4-methoxyphenyl)-3-oxopropanoate -Drug Synthesis Database

【结构式】

【分子编号】48551

【品名】ethyl 2-(4-methoxyphenyl)-3-oxopropanoate

【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：(III)

A new process for the production of venlafaxine has been reported: Esterification of 2-(4-methoxyphenyl)-acetic acid (I) with ethanol and sulfuric acid gives the corresponding ethyl ester (II), which is condensed with ethyl formate by means of NaH to yield 2-formyl-3-(4-methoxyphenyl)acetic acid ethyl ester (III). Reaction of (III) with dimethylamine and K2CO3 in EtOH affords 3-(dimethylamino)-2-(4-methoxyphenyl)acrylic acid ethyl ester (IV), which is reduced with either NaBH4, LiAlH4 or H2 over Pd/C or Pt/C in ethanol to provide the corresponding propionic ester (V). Finally, this compound is cyclized with the bismagnesiane (VI) in THF. Alternatively, acrylic ester (IV) can be obtained directly by condensation of acetate (II) with dimethylformamide diethylacetal (VII) at 135 C. Alternatively, propionic ester (V) can be obtained by condensation of acetate (II) with N,N-dimethylmethylene-iminium iodide (VIII) by means of LDA in THF/heptane/ ethylbenzene.

参考文献中间体

合成目标

【1】 Camps Garcia, P.; Bosch i Llado, J.; Onrubia Miguel, M.C.; Arnalot i Aguilar, C.; Soldevila Madrid, N. (Medichem SA); Venlafaxine production process. WO 0107397 .

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)	34793	2-(4-methoxyphenyl)acetic acid; p-Methoxyphenyl formate; Homoanisic acid; p-Methyl benzyl formate; 4-methoxyphenylacetic acid; 4-methoxybenzeneacetic acid; p-methoxyphenylacetic acid	104-01-8	C₉H₁₀O₃	详情	详情
(II)	48550	4-methoxyphenylacetic acid ethyl ester; Ethyl 4-methoxyphenylacetate; Homoanisic acid ethyl ester	14062-18-1	C₁₁H₁₄O₃	详情	详情
(III)	48551	ethyl 2-(4-methoxyphenyl)-3-oxopropanoate		C₁₂H₁₄O₄	详情	详情
(IV)	48552	ethyl (E)-3-(dimethylamino)-2-(4-methoxyphenyl)-2-propenoate		C₁₄H₁₉NO₃	详情	详情
(V)	48553	ethyl 3-(dimethylamino)-2-(4-methoxyphenyl)propanoate		C₁₄H₂₁NO₃	详情	详情
(VI)	48554	Pentamethylenebis(magnesium bromide); Pentane-1,5-di(magnesium bromide)		C₅H₁₀Br₂Mg₂	详情	详情
(VII)	31457	N-(diethoxymethyl)-N,N-dimethylamine; diethoxy-N,N-dimethylmethanamine	1188-33-6	C₇H₁₇NO₂	详情	详情
(VIII)	48555	Eschenmoser's salt; N,N-Dimethylmethyleneimmonium chloride; N,N-Dimethylmethyleneimmonium iodide		C₃H₈IN	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 cyclization of 3,5-dimethoxyaniline (I) with 2-formyl-2-(4-methoxyphenyl)acetic acid ethyl ester (II) by means of polyphosphoric acid trimethylsilyl ester (PPSE) by heating at 110 C gives the quinolone (III), which is alkylated with vinyl cyanide (IV) by means of Triton B in DMF to yield the propionitrile derivative (V). Finally, the cyano group of (V) is converted into the target tetrazolyl derivative by cyclization with tri-tert-butylstannyl azide in refluxing toluene.

参考文献中间体

合成目标

【1】 Joseph, B.; et al.; 3-Aryl-2-quinolone derivatives: Synthesis and characterization of in vitro and in vivo antitumor effects with emphasis on a new therapeutical target connected with cell migration. J Med Chem 2002, 45, 12, 2543.

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)	25780	3,5-dimethoxyaniline; 3,5-dimethoxyphenylamine	10272-07-8	C₈H₁₁NO₂	详情	详情
(II)	48551	ethyl 2-(4-methoxyphenyl)-3-oxopropanoate		C₁₂H₁₄O₄	详情	详情
(III)	46382	5,7-dimethoxy-3-(4-methoxyphenyl)-2(1H)-quinolinone		C₁₈H₁₇NO₄	详情	详情
(IV)	10847	Acrylonitrile	107-13-1	C₃H₃N	详情	详情
(V)	46383	3-[5,7-dimethoxy-3-(4-methoxyphenyl)-2-oxo-1(2H)-quinolinyl]propanenitrile		C₂₁H₂₀N₂O₄	详情	详情

Extended Information