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

Temperature

-70 °C

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%).

1. stirringwhile stirring
2. customThe layers were separated
3. extractionthe aqueous layer was extracted with dichloromethane (400 mL×2)
4. washThe combined organics were washed with a 20% aqueous solution of sodium tartrate (700 mL)
5. stirringThe organic phase was stirred with a 10% aqueous solution of sulfuric acid (800 mL) for 15 min
6. dry with materialThe organics were dried over sodium carbonate and sodium sulfate
7. concentrationconcentrated under reduced pressure
8. additionA saturated aqueous solution of sodium bisulfate (400 mL) was added to the residue
9. extractionthe mixture was extracted with ethyl acetate (100 mL×3)
10. extractionextracted with ethyl acetate (200 mL×3)
11. dry with materialThe combined organics were dried over sodium sulfate
12. concentrationconcentrated under reduced pressure

ORD record

ord-e12908ec255f4625ae4f032119ddd916

Source dataset

uspto-grants-2016_03

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09296745B2