Dimethylformamide → 2-Oxo-5-(trifluoromethyl)-1,2-dihydropyridine-3-carbaldehyde

Temperature

-78 °C

3-Bromo-5-(trifluoromethyl)pyridin-2-ol (8.20 g, 31.2 mmol) was added in small portions to a suspension of sodium hydride (0.8575 g, 33.94 mmol) in anhydrous THF (76 mL) at room temperature. After complete addition, the reaction mixture was cooled to −78° C. and treated with a 1.7 M solution of tert-butyllithium in pentane (40.0 mL) which was added dropwise via a syringe over a period of 15 min. After stirring for 5 min, anhydrous DMF (8.16 mL, 105 mmol) was added slowly while maintaining the temperature below −50° C. The reaction mixture was then stirred overnight allowing it to warm to room temperature. The resulting light brown mixture was quenched by addition of a saturated NH4Cl solution. The pH of the solution was adjusted to 9-10 by addition of aqueous NaHCO3. The resulting solution was extracted with EtOAc four times. The combined extracts were dried (MgSO4), filtered and concentrated to provide a brown solid crude product (7.33 g, >100% crude yield). MS calculated for C7H4F3NO2 (M+H)+192; found 192.1.

1. additionAfter complete addition
2. additionwas added dropwise via a syringe over a period of 15 min
3. temperaturewhile maintaining the temperature below −50° C
4. stirringThe reaction mixture was then stirred overnight
5. temperatureto warm to room temperature
6. customThe resulting light brown mixture was quenched by addition of a saturated NH4Cl solution
7. additionThe pH of the solution was adjusted to 9-10 by addition of aqueous NaHCO3
8. extractionThe resulting solution was extracted with EtOAc four times
9. dry with materialThe combined extracts were dried (MgSO4)
10. filtrationfiltered
11. concentrationconcentrated

ORD record

ord-69bc43f5fbc140e5b7a35ba12597cabc

Source dataset

uspto-grants-2007_12

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07307086B2