Methanol → 2-(2-Hydroxypropan-2-yl)isonicotinaldehyde

Participants

Reaction Conditions

Reaction Steps

To a solution of 2-(2-hydroxypropan-2-yl)isonicotinonitrile (41.4 g, 0.255 mol) in toluene (500 mL) was added dropwise a solution of diisobutylaluminum hydride (1 mol/L in hexane, 765 mL, 0.765 mol) at −70° C. over a period of 1.5 h. The reaction mixture was stirred at −70° C. for 30 min. Methanol (30 mL) was added followed by a 20% aqueous solution of sodium tartrate (700 mL) while stirring. The layers were separated and the aqueous layer was extracted with dichloromethane (400 mL×2). The combined organics were washed with a 20% aqueous solution of sodium tartrate (700 mL). The organic phase was stirred with a 10% aqueous solution of sulfuric acid (800 mL) for 15 min. The organics were dried over sodium carbonate and sodium sulfate and concentrated under reduced pressure. A saturated aqueous solution of sodium bisulfate (400 mL) was added to the residue and the mixture was extracted with ethyl acetate (100 mL×3). The aqueous layer was neutralized with aqueous sodium carbonate and extracted with ethyl acetate (200 mL×3). The combined organics were dried over sodium sulfate and concentrated under reduced pressure to afford the title compound (23 g, 54%).

Provenance & Evidence