Methyl 2- indole- 3 carboxylate

B. Methyl indole-4-carboxylate (30). A mixture of 7.0 g (28 mmol) of methyl trans-2-[ -(dimethylamino)vinyl]-3-nitrobenzoate(29) in 140 mL of dry benzene which contained 1.4 g of 10% Pd/C was shaken in a Parr apparatus under Hj (50 psi) for 1.5 h. The catalyst was removed by filtration, and the benzene solution was washed with 30 mL of 5% aq. HCl, brine and dried over MgS04. After removal of the solvent under reduced pressure, the residue was purified via chromatography on silica gel to furnish 6.9 g (82%) of methyl indole-4-carboxylate (30). 

The first indolization of an arylhydrazone was reported in 1983 by Fischer and Jourdan" by treatment of pyruvic acid 1-methylphenylhydrazone 3 with alcoholic hydrogen chloride. However, it was not until the following year that Fischer and Hess identified the product from this reaction as 1-methyl indole-2-carboxylic acid 4. 

This trend is also observed in the reactions with nitrogen- and carbon-centered nucleophiles (2001H425). Thus, the reaction of 109 with sodium indolyl in DMF affords methyl 2-(indol-l-yl)indole-3-carboxylate (188, 77%). In better yield, 2-(indol-l-yl)indole-3-carbaldehyde (189, 95%) is formed in the corresponding reaction (99H1157) of 115a (Scheme 28). Sodium imidazolyl reacts with 109 in DMF at 60°C to afford methyl 2-(imidazol-l-yl)indole-3-carboxylate (190,28%), methyl indole-3-carboxylate (191,11 %), and unreacted 109 (36%). In contrast, under the same conditions, 110 and 115a provide higher yields of methyl 2-(imidazol-... 

An excellent method for producing methyl indole-4-carboxylate from commercially available 3-nitro-2-methylbenzoic acid involves reduction of an intermediate nitroenamine (57). 

Condensation of aromatic methylesters such as methyl 4-methoxybenzoate 351 a or methyl 4-hydroxybenzoate 351b with excess sodium-HMDS 486 in a mixture of THF-l,3-dimethyl-imidazolin-2-one (DMEU) at 185 °C in a closed vessel affords 59 or 93% of 4-hydroxybenzonitrile 298 as well as 26% 352 with smooth cleavage of the aromatic methyl ether in 351a (Scheme 4.47). Methyl indole-3-carboxylate gives hkewise 3-cyanoindole in 81% yield [127] (cf. also ref [92] in section 4.3). 

In certain cases copper catalyzed processes might also be used for the N-alkynylation of azoles. Methyl indole-3-carboxylate was coupled with 1-bromo-2-triisopropylsilyl-acetylene in the presence of a copper-phenantroline catalyst to give the desired 1-ethynylindole derivative in excellent yield (6.74.),105... 

Pyrrole- and indole-carboxylic acid chlorides react with dialkyl- and diaryl-cadmium to yield the ketones and it is noteworthy that the reaction of the anhydride of indole-2,3-dicarboxylic acid with diphenylcadmium produces 3-benzoylindole-2-carboxylic acid and not its isomer (53JCS1889). The ability of l-methylindole-2-carboxylic acid to react with nucleophiles is enhanced by conversion into the mixed anhydride with methanesulfonic acid. The mixed anhydride reacts with carbanions derived from diethyl malonate and from methyl acetate to yield the indolyl (3- keto esters (80TL1957). 

Incorporation studies with isotopes showed that when anthranijate was converted to tryptophan, the carboxyl group df anthranilate was lost as carbon dioxide, but the nitrogen was retained. Because the enzymes in the tryptophan biosynthetic pathway have only a limited specificity, it was possible to substitute 4-methyl-anthranilate in E. coli extracts that could convert anthranilate to indole. This nonisotope label was conserved during the conversion to yield 6-methyl indole. 

Kaneko, C., Yamamoto, A. and Hashiba, M. (1979) Ring contraction reactions of methyl quinolyne 1-oxide 5-carboxylates via the corresponding benz[d]-3,l-oxazepines. A facile synthesis of methyl indole 4-carboxylate and its derivatives. Chemical e[ Pharmaceutical Bulletin, 27 (4), 946-952. 

The position of the sugar residue in the dihydroindole portion can be determined by methylation of the pigment with diazomethane and subsequent alkaline degradation of the resulting neobetanin derivative. In the case of 5-0-glycosides, 5-hydroxy-6-methoxyindole-2-carboxylic acid is obtained, whereas the 6-O-glyco-sides yield 6-hydroxy-5-methoxyindole-2-carboxylic acid (47,48). The indole carboxylic acids are easily identified by TIjC. 

SYNTHESIS OF INDOLES BY PALLADIUM-CATALYZED REDUCTIVE N-HETEROANNULATION OF 2-NITROSTYRENES METHYL INDOLE-4-CARBOXYLATE... 

C10H9NO2 methyl indole-4-carboxylate 39830-66-5 25 00 1.2355 2 19102 C10H10O 3-phenyl-2-butenal 1196-67-4 21.35 1.0453 2... 

C10H9NO2 methyl indole-3-carboxylate 942-24-5 25.00 1 2355 2 19104 C10H10O trans-4-phenyl-3-buten-2-one 1896-62-4 45.00 1.0097 1... 

C10H8O2 6-methyl-2H-1-benzopyran-2-one 92-48-8 577.15 51.344 1,2 18907 C10H9NO2 methyl indole-3-carboxylate 942-24-5 590.98 52.691 2... 

Merour, J.Y, and Cossais, E, Regioselective A-alkylation of methyl indole-2-carboxylate, Synth. Commun., 23, 1813, 1993. 

Direct 2-bromination of 3-substituted indoles can be carried out using N-bromosuccinimide in the absence of radical initiators. 2-Bromo- and 2-iodoindoles can be prepared very efficiently via a-lithiation (section 17.6.1) 2-haloindoles are also available from the reaction of oxindoles with phosphoryl halides. Bromination of methyl indole-3-carboxylate gives a mixture of 5- and 6-bromo derivatives. ... 

Both indoles were obtained as the methyl ethers. The chromophoric and physicochemical properties of 5,6-dimethoxyindole 13 and of 5,6-dimethoxyindole-2-carboxylic acid 23 (R = H) thus obtained were reported. As an extension of Raper s observations, Burton (32JCS546) reported the formation of the A-methyl indole 3 by oxidation of 3,4-dihydroxyphenylethylmethylamine with Ag20 and a simple synthesis of 5,6-dimethoxy-l-methylindole. 

Successful Baeyer-Villager oxidations have been reported for 5-chloroacetyl and 6-chloroacetyl derivatives of methyl indole-3-carboxylate and the corresponding 1-methyl derivatives <87H(26)1471>. The yields were much better for the chloroacetyl compounds than for the acetyl derivatives (Equation... 

Displayed below is the reaction route for the Reissert indole synthesis from c>-nitrotoluene and dimethyl oxalate, where the hydrolysis of methyl indole-2-carboxylate could be omitted, depending on the reaction conditions. 

For a structure-activity relationship study on 5/f-pyrido[4,3-(>]indoles (y-carbolines), we needed both 1-unsubstituted 271 and 1-substituted methyl 2,3-dihydro-3-oxo-5/f-pyrido[4,3-fc]indole -carboxylates 272 (Scheme 42). 

The Chi group further developed a highly enantioselective formal [4 + 2] cycloaddition of a-branched indole 3-carboxaldehydes with trifluoromethyl ketones or isatins to give polyeyelic and spiro lactones, respectively. The reaction is postulated to undergo a catalytic cycle of NHC-eatalyzed aetiva-tion of the C(sp )—H bond of 2-methyl indole 3-carboxaldehydes to produee ort/ o-quinodimethane intermediates. Notably, 2-methyl benzofuran and ben-zothiophene aldehydes are also suitable substrates for this reaction, while 2-methylbenzaldehyde gives the partially oxidized carboxylic acid under these conditions without the observation of the desired lactone product (Scheme 7.115). 

Somei and colleagues reported that 5-aminoisocoumarin was converted to methyl indole-4-carboxylate in excellent yield (Scheme 2, equation 1) [6]. This group also discovered that both 4- and 7-aminoindoles were obtained from the corresponding nitrocinnolines (equation 2) [7]. Echavarren... 

Ethyh5-Acetoxy-6-Bromo-2 (Bromomethyl)-1-Methyl Indole-3-Carboxylate (SI-4)... 

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