Synthesis
GENERAL STEPS: A dichloromethane (DCM) solution of 2M oxalyl dichloride (1.712 mL, 3.425 mmol) was added slowly and dropwise to ice-water-bath-cooled DCM (15 mL) under nitrogen protection. Subsequently, N,N-dimethylformamide (0.250 g, 3.425 mmol) was added dropwise and the reaction mixture was stirred at 0 °C for 30 min. Next, a solution of methyl 1H-indole-4-carboxylate (0.5 g, 2.854 mmol) in DCM (10 mL) was added. The reaction mixture was gradually warmed up to room temperature and stirring was continued for 1 hour. Upon completion of the reaction, the solvent was removed under reduced pressure. THF (15 mL) and 20% aqueous ammonium acetate were added to the residue and the mixture was stirred at reflux for 30 min at 70 °C. The reaction mixture was cooled and extracted with ethyl acetate. The organic phases were combined and concentrated under reduced pressure. The residue was purified by silica gel column chromatography with 90% ethyl acetate/hexane as eluent to afford methyl 3-formyl-1H-indole-4-carboxylate (551 mg, 95.0% yield) as a white solid.LCMS m/z = 204.2 [M + H]+. 1H NMR (400 MHz, CDCl3) δ ppm: 4.00 (s, 3H), 7.34 ( t, J = 7.8 Hz, 1H), 7.63 (dd, J = 8.0 and 1.0 Hz, 1H), 7.87 (dd, J = 7.5 and 1.0 Hz, 1H), 8.10 (d, J = 3.2 Hz, 1H), 9.08 (br s, 1H), 10.53 (s, 1H).
References
[1] Patent: WO2016/176177, 2016, A1. Location in patent: Page/Page column 81
[2] Patent: CN103772395, 2016, B. Location in patent: Paragraph 0053-0057
[3] Patent: WO2013/37960, 2013, A1. Location in patent: Page/Page column 82
[4] Bioorganic and Medicinal Chemistry Letters, 2007, vol. 17, # 6, p. 1793 - 1798
[5] Organic Letters, 2009, vol. 11, # 22, p. 5214 - 5217
