Dimethylformamide → tert-Butyl 4-chloro-3-formylpyridin-2-ylcarbamate

Temperature

-78 °C

Dissolve tert-butyl 4-chloropyridin-2-ylcarbamate (1.95 g, 0.00855 moles) in dry THF (50 mL) and cool to −78° C. under nitrogen atmosphere. Add dropwise 1.6 M n-BuLi/hexane (12.8 mL, 0.02053 moles) over a period of 15 minutes while maintaining the reaction temperature below −70° C. Stir the resulting red orange solution at −78° C. for 2 hours. Add DMF (3.3 mL, 0.04275 moles) dropwise to the reaction mixture while maintaining the reaction temperature below −70° C. Stir further at −78° C. for 2 hours and then quench the reaction mixture with saturated ammonium chloride (50 mL). Warm the reaction mixture to room temperature, extract with EtOAc (3×50 mL) and dry with MgSO4. Filter and concentrate under reduced pressure to afford a yellow viscous oil. Purify the crude product by flash column chromatography using 15-20% EtOAc/hexane to afford the title product as a white solid.

1. temperaturewhile maintaining the reaction temperature below −70° C
2. stirringStir further at −78° C. for 2 hours
3. customquench the reaction mixture with saturated ammonium chloride (50 mL)
4. temperatureWarm the reaction mixture to room temperature
5. extractionextract with EtOAc (3×50 mL)
6. dry with materialdry with MgSO4
7. filtrationFilter
8. concentrationconcentrate under reduced pressure
9. customto afford a yellow viscous oil
10. customPurify the crude product by flash column chromatography

ORD record

ord-b504d4fd05b54c95be18388f816a8c20

Source dataset

uspto-grants-2009_02

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07488740B2