Cesium carbonate → 4-Methoxy-2-(2H-1,2,3-triazol-2-yl)benzoic acid

Participants

Reaction Conditions

Reaction Steps

To 2-bromo-4-methoxybenzoic acid (4 g, 17.3 mmol), CuI (266 mg, 1.4 mmol) and Cs2CO3 (11.2 g, 34.6 mmol) was added dioxane (36 mL), water (94 μL, 5.1 mmol), 2H-1,2,3-triazole (2.0 mL, 34.6 mmol) and (1R,2R)—N1,N2-dimethylcyclohexane-1,2-diamine (683 μL, 4.3 mmol). The reaction mixture was heated to 100° C. for 3 hr. The reaction mixture was cooled rt, then EtOAc and water were added. The mixture was transferred to a separatory funnel and the aqueous layer separated. The aqueous layer was acidified with conc. HCl to pH˜2 and extracted with EtOAc (2×). The organic layers were washed with brine and dried (Na2SO4) to give a yellow solid. This material was slurried with EtOAc (˜20 mL) and the solids filtered (>95% 4-methoxy-2-(1H-1,2,3-triazol-1-yl)benzoic acid by HPLC). Purification (FCC) (50% DCM to 100% DCM containing 10% (5% formic acid/MeOH)) gave the title compound (2.6 g) as a yellow solid. 1H NMR (CDCl3): 7.99-7.90 (m, 1H), 7.83 (s, 2H), 7.20 (d, J=2.5 Hz, 1H), 7.03 (dd, J=8.8, 2.6 Hz, 1H), 3.89 (s, J=17.6 Hz, 3H).

Provenance & Evidence