ethyl 2-(4-aminophenyl)propanoate -Drug Synthesis Database

【结构式】

【分子编号】33984

【品名】ethyl 2-(4-aminophenyl)propanoate

【CA登记号】

【分子式】C₁₁H₁₅NO₂

【分子量】193.24564

【元素组成】C 68.37% H 7.82% N 7.25% O 16.56%

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 methylation of ethyl 4-nitrophenylacetate (I) with NaH - ICH3 in DMF - toluene to ethyl 2-(4-nitrophenyl)propionate (II), which was reduced with H2 over Pd/C in EtOH - H2O to ethyl 2-(4-aminophenyl)propionate (III) (HCl deriv., m.p. 137-40 C). This product was acetylated with acetic anhydride to ethyl 2-(acetylaminophenyl) propionate (IV), m.p. 88-90 C, which was chlorinated with Cl2 in acetic acid to ethyl 2-(3-chloro-4-acetylaminophenyl)propionate (V), b.p. 155-60 C/0.7 mm; this, in turn, was hydrolyzed with HCl in EtOH to ethyl 2-(3-chloro-4-aminophenyl)propionate hydrochloride (VI), m.p. 164-8 C. The last step being the reaction of the preceding intermediate with cis-1,4-dichloro (or dibromo)-2-butene (A) in DMF and Na2CO3 to ethyl 2-(3-chloro-4-(3-pyrrolinyl)phenyl)propionate (VII), b.p. 128-33 C/0.25 mm; followed by hydrolysis with KOH in EtOH - H2O. The acetylation of ethyl 4-aminophenylacetate (VIII) with acetic anhydride to ethyl 4-acetylaminophenylacetate (IX), m.p. 75-8 C, followed by methylation with ICH3 and Na in liquid NH3 to ethyl 2-(4-acetylaminophenyl)propionate (IV), already obtained.

参考文献中间体

合成目标

【1】 Carney, R.W.J.; de Stevens, G; Tertiary amino phenyl acetic acids. CH 574926; CH 577968; CH 578523; CH 581103; CH 581104; US 3641040 .
【2】 Castaner, J.; Pirprofen. Drugs Fut 1977, 1, 1, 23.

中间体序号	中间体编号	品名	CAS号	分子式	供应商	用于合成
(A)	32186	(E)-1,4-dichloro-2-butene	110-57-6	C₄H₆Cl₂	详情	详情
(I)	33982	ethyl 2-(4-nitrophenyl)acetate	5445-26-1	C₁₀H₁₁NO₄	详情	详情
(II)	33983	ethyl 2-(4-nitrophenyl)propanoate		C₁₁H₁₃NO₄	详情	详情
(III)	33984	ethyl 2-(4-aminophenyl)propanoate		C₁₁H₁₅NO₂	详情	详情
(IV)	33985	ethyl 2-[4-(acetamido)phenyl]propanoate		C₁₃H₁₇NO₃	详情	详情
(V)	33986	ethyl 2-[4-(acetamido)-3-chlorophenyl]propanoate		C₁₃H₁₆ClNO₃	详情	详情
(VI)	33987	ethyl 2-(4-amino-3-chlorophenyl)propanoate		C₁₁H₁₄ClNO₂	详情	详情
(VII)	33988	ethyl 2-[3-chloro-4-(2,5-dihydro-1H-pyrrol-1-yl)phenyl]propanoate		C₁₅H₁₈ClNO₂	详情	详情
(VIII)	21230	ethyl 2-(4-aminophenyl)acetate	5438-70-0	C₁₀H₁₃NO₂	详情	详情
(IX)	21231	ethyl 2-[4-(acetamido)phenyl]acetate		C₁₂H₁₅NO₃	详情	详情

合成路线2

该中间体在本合成路线中的序号：(I)

It can be obtained in two different ways, both starting from ethyl alpha-(4-aminophenyl)propionate (I): 1) The condensation of the amino compound (I) with benzaldehyde (A), followed by reduction of the Schiff base with H2 over Pt in ethanol gives ethyl alpha-(benzylaminophenyl)propionate (II), which by reaction with phosgene in toluene affords ethyl alpha-[N-chlorocarbonyl-(4-benzylaminophenyl)]propionate (III); the cyclization of this compound with AlCl3 in CH2Cl2 yields ethyl alpha-[4-(1-oxo-2-iso-indolinyl)phenyl]propionate (IV), which is finally saponified with K2CO3 in ethanol - water. 2) The cyclization of the amino compound (I) with 2-cyanobenzyl bromide (B) in refluxing ethanol affords ethyl alpha-[4-(1-imino-2-iso-indolinyl)phenyl]propionate (V). which is finally hydrolyzed and saponified with K2CO3 as before. The starting aminoester (I) is obtained as follows: The nitration of alpha-phenylpropionitrile (VI) gives alpha-(4-nitrophenyl)propionitrile (VII), which is hydrolyzed with H2SO4 to alpha-(4-nitrophenyl)propionic acid (VIII). Esterification of this acid with ethanol and H2SO4 yields ethyl alpha-(4-nitrophenyl)propionate (IX), which is finally reduced with H2 over Pd/C in ethanol giving the aminoester (I), b.p.(0.5mm) 125 C.

参考文献中间体

合成目标

【1】 Castaner, J.; Arrigoni, Martelli, E.; Indoprofen. Drugs Fut 1976, 1, 5, 242.
【2】 Nanini, G.; et al.; New analgesic-anti-inflammatory drugs. 1-oxo-2-substituted isoindoline derivatives. Arzneim-Forsch 1973, 23, Suppl. 3, 1090.

中间体序号	中间体编号	品名	CAS号	分子式	供应商	用于合成
(A)	10498	Benzaldehyde;Benzoic aldehyde;Phenylmethanal	100-52-7	C₇H₆O	详情	详情
(B)	33303	2-(bromomethyl)benzonitrile	22115-41-9	C₈H₆BrN	详情	详情
(I)	33984	ethyl 2-(4-aminophenyl)propanoate		C₁₁H₁₅NO₂	详情	详情
(II)	60734	ethyl 2-[4-(benzylamino)phenyl]propanoate		C₁₈H₂₁NO₂	详情	详情
(III)	60737	ethyl 2-{4-[benzyl(chlorocarbonyl)amino]phenyl}propanoate		C₁₉H₂₀ClNO₃	详情	详情
(IV)	60738	ethyl 2-[4-(1-oxo-1,3-dihydro-2H-isoindol-2-yl)phenyl]propanoate		C₁₉H₁₉NO₃	详情	详情
(V)	60739	ethyl 2-[4-(1-imino-1,3-dihydro-2H-isoindol-2-yl)phenyl]propanoate		C₁₉H₂₀N₂O₂	详情	详情
(VI)	60735	hydratroponitrile		C₉H₉N	详情	详情
(VII)	60736	2-(4-nitrophenyl)propanenitrile		C₉H₈N₂O₂	详情	详情
(VIII)	52520	2-(4-nitrophenyl)propanoic acid		C₉H₉NO₄	详情	详情
(IX)	33983	ethyl 2-(4-nitrophenyl)propanoate		C₁₁H₁₃NO₄	详情	详情

Extended Information