ethyl 4-chloro-1H-pyrrolo[2,3-b]pyridine-5-carboxylate

541-41-3

651744-48-8

885500-55-0

Under argon protection, 4-chloro-1-[tris(methylethyl)silyl ester]-1H-pyrrolo[2,3-b]pyridine (15 g, 48.6 mmol) was dissolved in tetrahydrofuran (THF) (150 mL) and cooled to -78 °C. A 1 M mixture of H-BuLi cyclohexane and hexane (97.1 mL, 97.1 mmol) was added slowly and dropwise. After stirring the reaction mixture at -78 °C for 1 h, ethyl chloroformate (9.29 mL, 97.1 mmol) was added. Stirring was continued at -78 °C for 30 min, followed by quenching the reaction with saturated aqueous NH4Cl and extraction with EtOAc. The combined organic phases were washed sequentially with water and brine, dried over anhydrous MgSO4 and concentrated under reduced pressure. The residue was dissolved in THF (120 mL) and 1M solution of TBAF THF (56 mL, 56 mmol) was added. After stirring for 1 h at room temperature, the reaction mixture was diluted with EtOAc, washed with water, dried over anhydrous MgSO4 and concentrated under reduced pressure. The residue was ground with isopropyl ether (IPE) and the precipitate was collected by filtration to afford ethyl 4-chloro-1H-pyrrolo[2,3-b]pyridine-5-carboxylate (9.6 g, 88% yield). Product characterization data: 1H-NMR (DMSO-d6) δ: 1.36 (3H, t, J=7.1 Hz), 4.36 (2H, q, J=7.1 Hz), 6.64-6.67 (1H, m), 7.70-7.73 (1H, m), 8.71 (1H, s), 12.41 (1H, br). m/z MS (ESI): 223 (M-H)-.