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0 °C

Starting material (5-bromo-6-chloropyridin-3-ol) is available from a published 3-step procedure: Synthesis, 1990, 499-501. To an oven-dried flask was added zinc (2.45 g, 37.4 mmol) and a crystal of iodine. The mixture was heated with a heat gun for 10 min under vacuum and then allowed to cool under Ar atmosphere. After charging the flask with degassed DMF (10 mL), the mixture was cooled to 0° C., and benzyl bromide (2.96 mL, 24.9 mmol) was added. After stirring the resulting mixture at 0° C. for 30 min, a mixture of Pd2(dba)3 (0.571 g, 0.624 mmol), S-Phos (1.02 g, 2.49 mmol) and 5-bromo-6-chloropyridin-3-ol (2.60 g, 12.5 mmol) was added to the flask quickly, and then the reaction was flushed with Ar and placed in an oil bath at 60° C. for 4 h or until starting material was gone by LCMS. The reaction was cooled to rt and filtered through a fine fritted funnel. The filtrate was concentrated to afford a yellow oil that was adsorbed onto silica and purified by flash chromatography (25% EtOAc/Hex, ramped to 100% EtOAc). The product was further purified after the column by recrystallization from hexane and minimal cold chloroform to afford a white solid. MS (ESI) m/z: Calculated: 219.1; Observed: 220.0 (M++1).

1. customSynthesis, 1990, 499-501
2. temperatureThe mixture was heated with a heat gun for 10 min under vacuum
3. temperatureto cool under Ar atmosphere
4. additionwas added to the flask quickly
5. customthe reaction was flushed with Ar
6. waitplaced in an oil bath at 60° C. for 4 h
7. temperatureThe reaction was cooled to rt
8. filtrationfiltered through a fine fritted funnel
9. concentrationThe filtrate was concentrated
10. customto afford a yellow oil that
11. custompurified by flash chromatography (25% EtOAc/Hex, ramped to 100% EtOAc)
12. customThe product was further purified after the column
13. customby recrystallization from hexane and minimal cold chloroform
14. customto afford a white solid