Hydrochloric Acid → HCID 24716972, compound

Participants

Reaction Steps

Phenylboric acid (2.13 g; 17.5 mmol) followed by KF solution (2M in water, 15 ml) and finally Pd(PPh3)4 (607 mg; 0.5 mmol; 3 mol %) were added under a nitrogen atmosphere to a solution of 6-bromoimidazo[1,2-a]pyridine-2-carboxylic acid ethyl ester (4.71 g; 17.5 mmol) in acetonitrile (30 ml) in a Milestone 100 ml high-pressure vessel. The reaction vessel was rinsed with nitrogen, closed and irradiated in a microwave at 160° C. for 5 min. (DC control: n-hexane-ethyl acetate 1:1). Two batches of the same size were run in parallel and combined prior to processing. The precipitated product was filtered out and washed with diethyl ether. The black crystalline product was taken up in chloroform and filtered first over silica gel and then over celite. The clear filtrate was concentrated to dryness. Yield: 9.3 g (100%). Stage 2. The 6-phenylimidazo[1,2-a]pyridine-2-carboxylic acid ethyl ester (9.32 g, 17.5 mmol) was dissolved in ethanol (80 ml) and NaOH solution (20% in water, 7 ml) was added. The reaction batch was refluxed for 8 hours. On completion of the reaction the solvent was removed in a rotary evaporator and the residue taken up in a small amount of water. The solution was carefully adjusted to pH 3-4 with HCl solution (10% in water). The precipitated product was filtered and washed with water and used in the next stage without further purification. Yield: 7.90 g (95%). Stage 3. Palladium on activated carbon (1.5 g) was added to a solution of 6-phenylimidazo[1,2-a]pyridine-2-carboxylic acid (6.3 g; 26.4 mmol) in a blend of HCl (4% in water, 100 ml) and ethanol (200 ml). The mixture was poured into an autoclave (stainless steel), the autoclave was closed and rinsed a few times with nitrogen. The autoclave was filled with hydrogen (8 bar) and the reaction batch stirred over the weekend at room temperature. The catalyst was filtered out over celite and the solvent drawn off in a rotary evaporator at room temperature. The product was crystallized out of acetonitrile. Yield: 4.1 g (56%).

Provenance & Evidence