Citric Acid → Methyl 1H-indazole-5-carboxylate

Participants

Reaction Conditions

Reaction Steps

To a solution of 5-bromo-3-methyl-1H-indazole (10 g, 47.6 mmol) in MeOH (160 mL), PdCl2.dppf (5.57 g, 7.62 mmol), NaOAc (11.7 g, 142.85 mmol) and DMF (5 mL) were added and degassed (using N2 gas 3-times). The mixture was sealed, charged with CO gas (60 psi) and heated at 80° C. for 20 hours. The reaction mixture was concentrated to obtain a residue, which was diluted with water (100 mL), acidified with 10% aqueous citric acid and extracted using ethyl acetate (3×200 mL). The combined organic layers were dried over anhydrous Na2SO4, filtered and concentrated to afford 1H-indazole-5-carboxylic acid methyl ester (7.23 g, 80%) as a solid. 1H NMR (CDCl3): δ 9.6-10.2 (br, 1H), 8.4-8.6 (s, 1H), 8.0-8.2 (d, 1H), 7.4-7.5 (d, 1H), 3.9-4.05 (s, 3H), 2.55-2.7 (s, 3H).

Provenance & Evidence