Cesium carbonate → 5-(Benzyloxy)-3-methyl-2-(propan-2-yloxy)pyridine-4-carboxylic acid

Participants

Reaction Conditions

Reaction Steps

A suspension of phenyl 5-(benzyloxy)-2-bromo-3-methylpyridine-4-carboxylate (2.4 g, 6.0 mmol) and Cs2CO3 (6.1 g, 19 mmol) in i-PrOH (36 mL) was degassed with N2 for 2 minutes. To the reaction mixture was added Pd2(dba)3 (0.31 g, 0.34 mmol) and t-Bu-BippyPhos (0.34 g, 0.66 mmol, cas:894086-00-1). The mixture was heated in the microwave at 115° C. for 1 hour. To the reaction mixture was added 4M NaOH (7 mL) and MeOH (7 mL) and the reaction mixture was stirred at 60° C. for 3 hours. The reaction mixture was concentrated under vacuum. To the residue was added EtOAc (60 mL) and H2O (80 mL). The aqueous layer was acidified with conc. HCl to pH 4 and extracted with EtOAc (2×40 mL). The combined organic layers were washed with brine (60 mL), dried over Na2SO4, and concentrated under vacuum to give 5-(benzyloxy)-3-methyl-2-(propan-2-yloxy)pyridine-4-carboxylic acid (131a, 1.1 g, 60%) as a yellow solid.

Provenance & Evidence