Acetic Anhydride → HCID 67976029, compound

Participants

Reaction Conditions

Reaction Steps

Methyl 3-amino-6-fluoro-2-methylbenzoate (7.50 g, 0.041 mol) was dissolved in 150 mL of acetic acid. To this was added acetic anhydride (14.6 g, 0.143 mol) and the mixture was warmed to 75° C. Sodium nitrite (11.3 g, 0.164 mol) was added in portions to the reaction mixture (evolution of an gas observed). The mixture was stirred at 75° C. for 16 hours, then allowed to cool to ambient temperature, and then poured into cold 10% aqueous potassium carbonate solution. This material was extracted twice with EtOAc, the extracts dried over sodium sulfate and concentrated under reduced pressure. Column chromatography (1:1 EtOAc/Hexanes) afforded 0.48 g of methyl 1-acetyl-5-fluoro-1H-indazole-4-carboxylate. The crude material was then added to 5 mL of 4M HCl/dioxane and 15 mL of methanol in a pressure tube and heated to 60° C. for 2 hours. The mixture was concentrated under reduced pressure and the resulting solids were taken up in 10% aqueous potassium carbonate/EtOAc. The organic layer was isolated, dried over sodium sulfate and concentrated under reduced pressure to give 0.483 g (5%) of the title compound.

Provenance & Evidence