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

【结构式】

【分子编号】33983

【品名】ethyl 2-(4-nitrophenyl)propanoate

【CA登记号】

【分子式】C₁₁H₁₃NO₄

【分子量】223.22856

【元素组成】C 59.19% H 5.87% N 6.27% O 28.67%

与该中间体有关的原料药合成路线共 3 条

合成路线1 合成路线2 合成路线3

合成路线1

该中间体在本合成路线中的序号：(II)

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：(IX)

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

合成路线3

该中间体在本合成路线中的序号：(VIII)

Ethyl 2-(4-nitrophenyl)propionate (VIII), obtained by acid-catalyzed esterification of carboxylic acid (VII), was alkylated by means of iodomethane and NaH to furnish the 2-methylpropionate (IX). Subsequent nitro group hydrogenation over Pd/C gave aniline (X). Diazotization of (X), followed by SnCl2 reduction of the intermediate diazonium salt, afforded the aryl hydrazine (XI). Cyclization between hydrazine (XI) and ketone (VI) under Fischer indolization conditions occurred with concomitant cyclopropyl group rearrangement to generate the racemic beta-methyl tryptamine derivative (XII), which was further separated into the enantiomers.

参考文献中间体

合成目标

【1】 Chu, L.; Wyvratt, M.J.; Ponpipom, M.M.; Lin, P.; Ashton, W.T.; Goulet, M.; Young, J.; Girotra, N.N.; Fisher, M.H. (Merck & Co., Inc.); Antagonists of gonadotropin releasing hormone. EP 1095038; WO 0004013 .

中间体序号	中间体编号	品名	分子式	供应商	用于合成
(VI)	52519	(3,5-dimethylphenyl)(2-methylcyclopropyl)methanone	C₁₃H₁₆O	详情	详情
(VII)	52520	2-(4-nitrophenyl)propanoic acid	C₉H₉NO₄	详情	详情
(VIII)	33983	ethyl 2-(4-nitrophenyl)propanoate	C₁₁H₁₃NO₄	详情	详情
(IX)	52521	ethyl 2-methyl-2-(4-nitrophenyl)propanoate	C₁₂H₁₅NO₄	详情	详情
(X)	52522	ethyl 2-(4-aminophenyl)-2-methylpropanoate	C₁₂H₁₇NO₂	详情	详情
(XI)	52523	ethyl 2-(4-hydrazinophenyl)-2-methylpropanoate	C₁₂H₁₈N₂O₂	详情	详情
(XII)	52524	ethyl 2-[3-(2-amino-1-methylethyl)-2-(3,5-dimethylphenyl)-1H-indol-5-yl]-2-methylpropanoate	C₂₅H₃₂N₂O₂	详情	详情

Extended Information