Methanol → HCID 67334590, compound

Participants

Reaction Steps

To a solution of 2-bromo-3-hydroxy-6-iodopyridine (8-2, 10 g, 33.3 mmol, 1.0 equiv) in DMF (104 ml) was added TBAI (1.23 g, 3.33 mmol, 0.1 equiv), diisopropylethylamine (17.5 mL, 100 mmol, 3.0 equiv) and SEM-Cl (8.87 mL, 50.0 mmol, 1.5 equiv). The system was stirred at ambient temperature for 24 hours. The reaction was partitioned between EtOAc and saturated NaHCO3. The organic phase was washed with NaHCO3 and dried over MgSO4. After concentration, the residue was purified by normal phase column chromatography (0 to 50% EtOAc in hexanes) to afford a pale yellow oil. To this pale yellow oil in DMF (145 mL) was added a 4.37M solution of NaOMe in MeOH(6.65 mL, 29.1 mmol, 1.0 equiv) and the system was heated to 100° C. for 1 hour. The system was cooled to ambient temperature and partitioned between EtOAc and saturated NaHCO3. The organic phase was washed with brine and dried over MgSO4. After concentration, the residue was purified by normal phase column chromatography (0 to 20% EtOAc in hexanes) to afford a clear oil. To this clear oil in DMF (69 mL) was added CuCN (3.71 g, 41.4 mmol, 2.0 equiv) and the system was irradiated at 160° C. for 0.5 hour. The reaction mixture was filtered through celite and partitioned between EtOAc and brine. The organic phase was dried over MgSO4 and concentrated. The residue was purified by normal phase column chromatography (0 to 50% EtOAc in hexanes) to afford a yellow solid. ESI+MS[M+H]+C7H6N2O2=151.0

Provenance & Evidence