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

Participants

Reaction Conditions

Reaction Steps

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)+.

Provenance & Evidence