Indole-2-carboxylic ester, 1-hydroxy

In a Nenintzescu indole synthesis with 2-alkyl-l,4-benzoquinones (3) and 3-aminocrotonates (4) (Scheme 1), two isomeric products (5) and (6) were formed. The compound 5 was already identified as 5-hydroxy-6-alkylindole-3-carboxylic ester. For compound 6, there was ambiguity as to whether there was 4- or 7- alkyl substitution. The following solution was obtained ... 

Indole-2-carboxylic acid, 5-hydroxy-ethyl ester acylation, 4, 219... 

Esters of 2-(2-azidophenyl)ethyl alcohol are photolyzed under a high-pressure mercury lamp to a reactive nitrene intermediate which, following insertion into the alkyl side-chain, undergoes elimination to give the free carboxylic acid (up to 32%) and producing indole. The photochemical release was somewhat improved (65-80%) when 5-azido-4-(hydroxy-methyl)-l-methoxy naphthalene was used (see Scheme 27). 

CPB3678) and the ester (Table IV) show that these compounds exist entirely as the hydrogen-bonded 1-hydroxy tautomers, but in contrast, 3-bromo-l-hydroxyindole-2-carboxylic acid appears to favor the 3H-indole 1-oxide form [68JCS(C)504]. Only the 1-hydroxy tautomer was observed in a number of cases in deuteriochloroform and in hexadeuterio-dimethylsulfoxide solutions (83JOC3639). 

To a solution of the S-(+)-4-acethoxy-9-[2-(5-ethyl-l,2,3,6-tetrahydro-pyridin-3yl)-l-(lH-indol-2-yl)-l-methoxycarbonyl-ethyl]-3a-ethyl-5-hydroxy-8-methoxy-6-methyl-3a,4,5,5a,6,ll,12,12b-octahydro-lH-6,12a-diaza-indeno[7,l-ca]fluorene-5-carboxylic acid methyl ester in dioxane and glacial acetic acid was added 37% aqueous formaldehyde and the mixture stirred at 35°C for 24 h. The solution was evaporated in vacuo and the residue suspended in chloroform and washed with cold aqueous 5% K2C03 solution. The chloroform layer was dried (MgS04), filtered, and evaporated. The residue was chromatographed eluting with EtOAc/MeOH, 10% NH4OH to give the product navelbine. 

The Martinet procedure for the synthesis of indole-2,3-diones involves the reaction of an aminoaromatic compound and either an oxomalonate ester or its hydrate in the presence of an acid to yield a 3-(3-hydroxy-2-oxindole)carboxylic acid derivative which after oxidative decarboxylation yields the respective isatin. This method was applied with success for the synthesis of 5,6-dimethoxyisatin from 4-aminoveratrole whereas the use of 2,4-dimethoxyaniline was less successful40 (Scheme 9). 

Hydroxy-2-methyl-1 H-indole-3-carboxylic acid ethyl ester... 

Synthesis of Aromatic Nitriles from Esters. A one-flask method has been developed for the conversion of aromatic esters to the corresponding nitriles by use of NaHMDS in a sealed tube at 185 °C in a mixture of THF and 1,3-dimethyl-2-imidazolidinone (DMEU) (eq 20). The transformation proceeded with good to excellent yields. The synthetic strategy is only apphcable to aromatic esters that bear an electron-donating substituent such as hydroxy or methoxy. In the latter case, con tetitive 0-demethyla-tion is observed, thus leading to a mixture of nitrile products. The reaction has been also applied to indole-3-carboxylate. However, simple unsubstituted methyl benzoate failed to give the desired product. 

Substituted 7,12-dihydroindolo[3,2-c(][l]benzazepin-6(5/0ones 2a and 2b were first reported in 1958 by MacPhillamy et al. [33] as the last intermediate in an 11-step synthesis of 4-ethyl-5,6,7,12-tetrahydro-2-methylindolo[3,2-t/][l]benzazepine. In 1992, Kunick reported the preparation of six indolo[3,2-d][l]benzazepin-6(5/f)ones [34] in a three-step procedure. The crucial step was the decarboxylation reaction of 2,3-dihydro-5-hydroxy-2-oxo-l/7-benz[(t]azepin-4-carboxylic acid ethyl ester into 3,4-dihydro-lH-benz[ ]azepin-2,5-dione, which made possible the subsequent Fischer indole synthesis, with formation of the desired 7,12-dihydroindolo[3,2-fiT [l]benzazepin-6(5/f)ones. 

C111H15N3O5 0.5 CH4O, 3-Carbamoyl-1,2-dihydro-4-hydroxy-5-methoxy-3H-pyrrolo[3,2-e]indole-7-carboxylic acid methyl ester methanol solvate, 44B, 255... 

Hydroxy-1//-indole-2-carboxylic acid Me ether, Et ester, in H-00253... 

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