Indole-1,3-dicarboxylic acid 1-tert-butyl ester 3-methyl ester

Synthesis

Methyl indole-3-carboxylate (17.1 mmol) was placed in a 50 mL round-bottomed flask, NaH (1.5 eq.) was added and cooled under ice bath conditions. THF (20 mL) was added slowly and stirred for 30 minutes. Subsequently, di-tert-butyl dicarbonate (1.5 eq.) was added and the reaction continued to stir overnight. Upon completion of the reaction, the reaction was quenched with saturated NaHCO3 solution, the reaction mixture was diluted with ether and washed with water. The organic layer was dried with anhydrous Na2SO4 and concentrated. The crude product was purified by column chromatography (ethyl acetate/hexane as eluent) to give 3-methyl-1H-indole-1,3-dicarboxylic acid-1-tert-butyl ester in 98% yield.

References

[1] Patent: US2009/215828, 2009, A1. Location in patent: Page/Page column 13
[2] Patent: WO2009/103552, 2009, A1. Location in patent: Page/Page column 31
[3] Research on Chemical Intermediates, 2017, vol. 43, # 3, p. 1355 - 1363
[4] Tetrahedron, 2003, vol. 59, # 6, p. 747 - 754
[5] Chemistry - A European Journal, 2010, vol. 16, # 48, p. 14534 - 14544