Potassium Carbonate → HCID 86653033, compound

Participants

Reaction Conditions

Reaction Steps

A mixture of 2-chloro-8-methylquinoline-3-carboxaldehyde (234 mg, 1.14 mmol), 2-thiopheneboronic acid (248 mg, 1.94 mmol), K2CO3 (315 mg, 2.28 mmol), palladium(II) acetate (10 mg, 0.045 mmol) and triphenylphosphine (48 mg, 0.182 mmol) in water (2 mL) was degassed. 1,4-Dioxane (6 mL) was added and the mixture further degassed, then heated at 115° C. for 2 h under microwave irradiation. The reaction mixture was filtered through Celite, washed with DCM and water and the filtrate was concentrated in vacuo. The residue was partitioned between DCM (100 mL) and H2O (50 mL). The aqueous layer was re-extracted with DCM (50 mL) and the combined organic layers were dried (MgSO4) and concentrated in vacuo. Purification by column chromatography (SiO2, DCM) gave 8-methyl-2-(thien-2-yl)quinoline-3-carboxaldehyde (219 mg) as a yellow solid. This was dissolved in MeOH/DCM (6 mL/3 mL) and to it was added sodium borohydride (59 mg, 1.56 mmol). The reaction mixture was stirred at room temperature, quenched by the addition of glacial AcOH (0.1 mL) and the solvent removed in vacuo. The residue was partitioned between DCM (200 mL) and 5% aqueous Na2CO3 solution (40 mL). The aqueous layer was re-extracted with DCM (60 mL) and the combined organic layers were dried (MgSO4) and concentrated in vacuo. Purification by column chromatography (SiO2, 3% EtOAc in DCM) gave the title compound as a yellow solid (110 mg, 38%). δH (CDCl3) 8.27 (s, 1H), 7.70 (d, J 6 Hz, 1H), 7.65 (d, J 12 Hz, 1H), 7.55 (d, J 12 Hz, 1H), 7.48 (d, J 9 Hz, 1H), 7.36-7.45 (m, 1H), 7.15-7.20 (m, 1H), 5.10 (d, J 5.8 Hz, 2H), 2.85 (s, 3H), 1.94 (t, J 12 Hz, 1H). LCMS (ES+) 256.2 (M+H)+, RT 4.06 minutes (Method 4).

Provenance & Evidence