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

Temperature

-78 °C

Under nitrogen, the compound from Step A above (48.8 g, 202 mmol) was added in small portions to a suspension of sodium hydride (8.9 g, 220 mmol) in anhydrous tetrahydrofuran (500 mL). After complete addition of the intermediate, the reaction mixture was cooled to −78° C. and treated with tert-butyllithium (260 mL, 444 mmol) added dropwise via syringe. After stirring for 5 min, N,N-dimethylformamide (50 mL, 707 mmol) was added slowly, maintaining the temperature below −50° C. The resultant mixture was allowed to slowly warm to room temperature over 10 h. The mixture was quenched with 2N hydrochloric acid and then diluted with ethyl acetate (1000 mL). The organic layer was separated, washed with saturated brine, dried over magnesium sulfate and evaporated in vacuo. The desired product was precipitated out of a mixture of ethyl acetate and hexanes and filtered to yield a light brown solid.

1. additionAfter complete addition of the intermediate
2. additionadded dropwise via syringe
3. temperaturemaintaining the temperature below −50° C
4. temperatureto slowly warm to room temperature over 10 h
5. customThe mixture was quenched with 2N hydrochloric acid
6. additiondiluted with ethyl acetate (1000 mL)
7. customThe organic layer was separated
8. washwashed with saturated brine
9. dry with materialdried over magnesium sulfate
10. customevaporated in vacuo
11. customThe desired product was precipitated out of a mixture of ethyl acetate and hexanes
12. filtrationfiltered
13. customto yield a light brown solid

ORD record

ord-f7011ef973684f8282791ae108502b01

Source dataset

uspto-grants-2008_06

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07388019B2