Tetrahydrofuran → 1H-Indazole-6-carbaldehyde

Participants

Reaction Steps

To a suspension of 60% NaH (10.0 g, 0.24 mol) in THF (240 mL) was added a suspension of 6-bromo-1H-indazole (39.4 g, 0.2 mol) in THF (280 mL) dropwise over 45 min. After addition, the resulting mixture was stirred for 1 h at rt to give a dark red clear solution which was cooled to −78° C. s-BuLi (1.4 M in hexane, 300 mL, 0.42 mol) was added dropwsie over 1 h. During this addition, additional THF (130 mL) was added to keep the mixture stirring. After the addition, the resulting mixture was stirred for 75 min at −78° C.; DMF (90 mL) was added dropwise (note: reaction solidified upon addition of DMF, occasional warming was needed to keep the mixture stirring). The resulting mixture was stirred at rt overnight and cooled to 0° C. Solid NH4Cl and saturated NH4Cl were added to quench the reaction and bring the pH to about 7. The product was extracted with EtOAc (800 mL+200 mL+300 mL, 1.3 L in total) and the combined extracts were washed with H2O (300 mL×3) and dried (Na2SO4). Evaporation of the solvent gave a dark red solid which was triturated by EtOAc (4 times, the last filtrate was purified by flash chromatography) to give the title compound (16.96 g in total, 58%) as yellow brown solid. 1H NMR (400 MHz, DMSO-d6) δ 13.62 (s, 1H, NH), 10.12 (s, 1H, CHO), 8.23 (s, 1H), 8.17 (s, 1H), 7.93 (d, J=8.4 Hz, 1H), 7.59 (d, J=8.4 Hz, 1H); MS ESI 147.0 [M+H]+, calcd for [C8H6N2O+H]+ 147.0.

Provenance & Evidence