ETHYL 2-METHYLINDOLE-5-CARBOXYLATE

C. Ethyl 2-methylindole-5-carboxylate. A solution of lO.Og. (0.040 mole) of ethyl 2-methyl-3-methylthioindole-5-carboxylate in 300 ml. of absolute ethanol is placed in a 500-ml., three-necked, round-bottomed flask fitted with a mechanical stirrer. An excess (15 teaspoons) (Note 11) of freshly washed W-2 Raney nickel (Note 12) is added, and the mixture is stirred for one hour. Stirring is then stopped, the liquid phase is decanted, and the catalyst is washed twice by stirring for 15 minutes with 100-ml. portions of absolute ethanol and decanting the solvent. The combined ethanolic solutions are concentrated on a rotary evaporator, and the residual solid is dissolved in 150 ml. of warm dichloromethane. This solution is dried over anhydrous magnesium sulfate and filtered, and the drying agent is washed with 40 ml. of dichloromethane. Concentration of the combined filtrates with a rotary evaporator gives... 

In 1929, Nenitzescu reported that p-benzoquinone (4) was treated with ethyl 3-aminocrotonate (5) in boiling acetone to yield ethyl 5-hydroxy-2-methylindole-3-carboxylate (6). ... 

Heating pyridine-2,3-dicarboxylic acid anhydride with l-ethyl-2-methylindole has been claimed to yield solely the pyridine-2-carboxylic acid, albeit in low yield. This then clearly reacts with Af,A/-diethyl-3-toluidine in acetic anhydride to give the 7-azaphthalide. This is surprising in view of a later report70 in which a one-pot process has been described. Heating pyridine-2,3-dicarboxylic anhydride, prepared in situ, with the indole and subsequent reaction with 3-/V,/V-diethylamino-phenetol under identical conditions to those used in Scheme 8 (but without intermediate isolations) produced a 20 1 mixture of the 4- and 7-azaisomers 16 and 17. It appears that in the previous report the major intermediate isomer, the pyridine-3-carboxylic acid, has not been isolated. 

Pyrroles and furans also undergo the Gattermann aldehyde synthesis with HC1 and HCN, furan gives furfuraldehyde and 2-methylindole gives 2-methylindole-3-carboxaldehyde. The Houben-Hoesch ketone synthesis is also applicable to the preparation of acyl derivatives of furans and pyrroles, e.g. ethyl 2,4-dimethylpyrrole-3-carboxylate with MeCN and HC1 yields (81). 

In a reaction, the mechanism of which bears a close analogy with that shown for the phenyl group migration in Scheme 18, ethyl 3-methylindole-2-carboxylate is converted by sulfuryl chloride into ethyl 3-methyl-2-oxoindoline-3-carboxylate (79JCS(P1)595). 

In contrast with the relatively facile nucleophilic substitution reactions at the 2-position of the indole system, only 3-iodoindole has been reported to react with silver acetate in acetic acid to yield 3-acetoxyindole (59JOC117). This reaction is of added interest as 3-iodo-2-methylindole fails to react with moist silver oxide (72HC(25-2)127). It is also noteworthy that the activated halogen of ethyl 3-bromo-4-ethyl-2-formylpyrrole-5-carboxylate is not displaced during the silver oxide oxidation of the formyl group to the carboxylic acid (57AC(R)167>. 

Ethyl 2-[(S)-l-(Benzyloxycarbonylamino)-3-methylbutyll-5-(l-methylindol-3-yl)oxazole-4-carboxylate... 

Ifenprodil (= l-Methyl-2-hydroxy-2-(4-hydroxyphenyl) ethyl-1 -(4-benzyl-piperidine)] -(aryl piperidine) [at(/o-3-(Indol-2-yl)-8-methyl-8-azabicyclo-[3.2.1] octane] (indolotropane) [Kynurenic acid (= 4-Hydroxy-2-quinolinecarboxylic acid)] (quinoline carboxylic acid) [Memantine (= 1-Amino-3,5 dimethyladamantane)] (amino adamantane, amino cyclic aliphatic) [Methadone (= 6-Dimethylamino-4,4-diphenyl-3-heptanone)] (aryl tertiary amine) [em/o-3-(l -Methylindol-2-yl)-8-methyl-8-azabicyclo-[3.2.1] octane(indolotropane) exo- 3-( 1 -Methylindol-2-yl)-8-methyl-8-... 

C12H12N2 1,1 diphenylhydrazine 530-50-7 582.21 51.836 2 23856 C12H13N03 ethyl 5-hydroxy-2-methylindole-3-carboxylate 7598-91-6 568.15 50.469 2... 

J.M. Cook et al. accomplished the enantiospecific total synthesis of the indole alkaloid tryprostatin A." The substituted indole nucleus was assembled at the beginning of the synthesis, and the necessary arylhydrazone was prepared via the Japp-Kiingemann reaction using the diazonium salt derived from m-anisidine and the anion of ethyl-a-ethylacetoacetate. The regioselectivity of the Fischer indoie synthesis favored the 6-methoxy-3-methylindole-2-carboxylate regioisomer in a 10 1 ratio. 

Thus irradiation of ethyl 2-cyano-4-methyl-l,2-dihydroquinoline-l-carboxylate (3a) in diethyl ether with a 350-W high-pressure mercury lamp through a Pyrex filter gave a cyclopropaindole as minor product, along with ethyl 2-cyanomethyl-3-methylindole-l-carboxylate arising from the intramolecular cyclization of an allene intermediate. 

In another study (82JOC5258), air oxidation of a-methyl-3,4-dihydroxyphenyl-alanine ethyl ester was shown to lead to ethyl 5,6-dihydroxy-2-methylindole-3-carboxylate 31 via a remarkable 1,2-migration of the ethoxycarbonyl group of the aminochrome intermediate (Eq. (4)). The structure of the product was confirmed by an independent synthesis ... 

Pyrrole ring. Ene-l,2-di(oxysilanes) can be used in place of acyloins for the synthesis of various heterocyclics. - E l,2-Bis(trimethylsiloxy)cyclohexene, ethyl /9-aminocrotonate, and glacial acetic acid heated 1 hr. at 100° ethyl 4,5,6,7-tetrahydro-2-methylindole-3-carboxylate. Y 96%. F. e. and heterocyclics s. K. Riihlmann et al., J. pr. 311, 844 (1969). 

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