2-Chloro-4-pyridinecarboxaldehyde → HCID 59853074, compound

Temperature

0 °C

To a solution of tert-butyl 4-bromo-3-fluorophenylcarbamate (2.60 g, 9.0 mmol) in anhydrous THF (30 mL) at −78° C. was added MeMgBr (3.0 M in Et2O, 3.1 mL, 9.3 mmol) via syringe. The solution was stirred for 10 min at that temperature, and then warmed to 0° C. for 0.5 h. After the solution was cooled back to −78° C., a solution of t-BuLi (1.7 M in hexane, 10.6 mL, 18.1 mmol) was added over 4 min. The resulting solution was allowed to stir for 5 min before a solution of 2-chloroisonicotinaldehyde (1.41 g, 10 mmol) (for preparation, see Frey, L. F. et al. Tetrahedron Lett. 2001, 42, 6815) in anhydrous THF (25 mL) was added in 3 min. The reaction mixture was stirred at −78° C. for 20 min and 2.0 mL of MeOH was added. The solution was then concentrated under reduced pressure and the residue was dissolved in 200 mL of EtOAc. It was subsequently washed with H2O (2×50 mL), brine (2×50 mL) and dried over MgSO4. After filtration and concentration, the residue was purified by flash chromatography on SiO2 eluting with 0%-50% EtOAc in hexane to give tert-butyl 4-((2-chloropyridin-4-yl)(hydroxy)methyl)-3-fluorophenylcarbamate (1.30 g, 41% yield). MS (ESI+): m/z 353.28/355.24 (M+H)+.

1. temperatureAfter the solution was cooled back to −78° C.
2. additionwas added in 3 min
3. stirringThe reaction mixture was stirred at −78° C. for 20 min
4. concentrationThe solution was then concentrated under reduced pressure
5. dissolutionthe residue was dissolved in 200 mL of EtOAc
6. washIt was subsequently washed with H2O (2×50 mL), brine (2×50 mL)
7. dry with materialdried over MgSO4
8. filtrationAfter filtration and concentration
9. customthe residue was purified by flash chromatography on SiO2 eluting with 0%-50% EtOAc in hexane

ORD record

ord-6fc6b444046d489994cb5fdbd8be5b9b

Source dataset

uspto-grants-2011_08

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07989477B2