1) Oxidation of 6-(Hydroxymethyl)pyridin-3-ol

SyntheticPage 549
Published Apr 06, 2012

Reaction Scheme

Procedure

6-(Hydroxymethyl)pyridin-3-ol (6.74 g, 53.86 mmol, 1.0 eq.) was dissolved in isopropanol (200 ml) to give a brown solution. Activated manganese(IV) oxide (11.71 g, 86.94 mmol, 2.5 eq.) was then added as a solid. The black mixture was stirred at reflux (100°C) for 4 h and then stirred at ambient temperature for a further 18 h. The solution was filtered through celite and the remaining MnO2 was washed with isopropanol (5 × 150 ml). The solvent was removed from the filtrate under reduced pressure to leave a yellow-brown solid. The solid was recrystallised from hot water (~ 20 ml) to leave the pure product as brown crystals. Yield = 3.99 g, 32.41 mmol, 60%.

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2) Williamson etherification using a hydroxypyridine

SyntheticPage 555
Published Apr 16, 2012

Reaction Scheme

Procedure

Potassium carbonate (0.59 g, 4.26 mmol, 1.05 eq.) was added to a solution of 5-(hydroxy)picolinaldehyde (0.50 g, 4.06 mmol, 1.0 eq.) in DMF (15 ml). Propargyl bromide (80% in toluene, 0.475 ml, 4.26 mmol, 1.05 eq.) was added to the reaction via syringe. The round bottomed flask was fitted with a condenser and the solution was stirred at 100°C for 4 h before allowing to cool to ambient with stirring for an additional 1 h. The solvent was then removed under reduced pressure. The crude solid was then taken up in chloroform (150 ml) and filtered. This process was repeated a further two times (2 × 40 ml). The chloroform was then removed from the filtrate under reduced pressure to leave an orange solid, which was dried overnight in vacuo. Yield = 0.32 g, 1.99 mmol, 49%.

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