Ethyl indole-2-carboxylate

Ethyl o-nitrocinnamate (1 mmol) was dissolved in triethyl phosphite (5 mmol) and heated at 170°C for 3 h. The triethyl phosphite and triethyl phosphate were removed in vacuo. The residue w as eluted through a column of silica gel using CHCI3 and the product recrystallizcd from CHCl3-hexane. The yield was 94%. 

ETHYL INDOLE-2-C ARBO XYLATE (Indole-2-carboxylic acid, ethyl ester) 

Submitted by Wayland E. Noland and Frederic J. Baude.1 Checked by E. J. Corey and Ronald J. McCadlly. 

Potassium salt of ethyl o-nitrophenylpyruvate. Anhydrous ether (300 ml.) is placed in a 5-1., three-necked, round-bottomed 

The dried ester can be further purified by treatment with charcoal and recrystallization from a mixture of methylene chloride and light petroleum ether (b.p. 60-68°). This gives 11.3-11.7 g. (41-44% based on o-nitrotoluene) of ethyl indole-2-carboxylate in the form of white needles, m.p. 122.5-124° (Note 5). 

Complete solution of the potassium takes 1.5-2 hours with stirring and 2.5-3 hours without stirring. 

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Ethyl indole-2-carboxylate 3-(Methoxycarbonyl)propanoyl chloride, AICI3, nitrobenzene 95 [10]... 

Ethyl indole-2-carboxylate 4-Methoxybenzoic acid, TFAA, H3PO4 74 [11]... 

A traditional method for such reductions involves the use of a reducing metal such as zinc or tin in acidic solution. Examples are the procedures for preparing l,2,3,4-tetrahydrocarbazole[l] or ethyl 2,3-dihydroindole-2-carbox-ylate[2] (Entry 3, Table 15.1), Reduction can also be carried out with acid-stable hydride donors such as acetoxyborane[4] or NaBHjCN in TFA[5] or HOAc[6]. Borane is an effective reductant of the indole ring when it can complex with a dialkylamino substituent in such a way that it can be delivered intramolecularly[7]. Both NaBH -HOAc and NaBHjCN-HOAc can lead to N-ethylation as well as reduction[8]. This reaction can be prevented by the use of NaBHjCN with temperature control. At 20"C only reduction occurs, but if the temperature is raised to 50°C N-ethylation occurs[9]. Silanes cun also be used as hydride donors under acidic conditions[10]. Even indoles with EW substituents, such as ethyl indole-2-carboxylate, can be reduced[ll,l2]. 

Ethyl indole-2-carboxylate (45.2 g, 0.238 mmol) was dissolved in abs. EtOH (450 ml) in a 11 polyethylene container and cooled in a dry icc-cthanol bath. The solution was saturated with dry HCl gas until the volume increased to 875 ml, Granular tin metal (84.2g, 0.7l0mmol) was added to the slurry and... 

Alkaline hydrolysis of ethyl indole-2-carboxylate yields indole-... 

Ethyl indole-2-carboxylate, 43,40 Ethyl isocyanide, 41, 15 N-Ethyi-N-methylaniline, 43,47 Ethyl o-nitrophenylpyruvate, potassium salt of, 43, 40... 

Reductive cyclization of the potassium salt of ethyl o-nitrophenylpyru-vate to ethyl indole-2-carboxyl-ate, 43, 40... 

A semisystematic study into the hydrolysis of ethyl indole-2-carboxylate in aqueous media at high temperature, indicated that decarboxylation of the resultant acid proceeded by an arenium ion mechanism and was inhibited by base. As base pro-... 

Alternatively, diazotization of ethyl indole-2-carboxylate (179) leads to formation of 2-carboethoxy-3-diazo-3H-indole (180) which undergoes rhodium-catalyzed alcohol O-H insertion reactions leading to 3-alkoxyindoles 181 <00TL6905>. 

Synthetic approaches toward mitomycin analogs have prompted the preparations of many benzopyrrolizines.46 49 One involved base-catalyzed 1,4-addition of ethyl indole-2-carboxylates (67) to an acrylic ester, followed by... 

Ethyl indole-2-carboxylate Acetic acid Acetic anhydride Hydrogen... 

Indole synthesis. In the first step of the synthesis o-nitrotoluene is condensed with diethyl oxalate in the presence of potassium ethoxide, and the product is isolated as the deep purple potassium enolate. Hydrogenation in acetic acid reduces the nitro group and effects cyclization to ethyl indole-2-carboxylate. This on hydrolysis and decarboxylation affords indole. 

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