tert-Butyl (4-chloro-3-formylpyridin-2-yl)carbamate

130721-78-7

68-12-2

868736-42-9

The general procedure for the synthesis of tert-butyl 4-chloro-3-formylpyridine-2-carbamate from 2-BOC-amino-4-chloropyridine and N,N-dimethylformamide was as follows: firstly, tert-butyl (4-chloropyridin-2-yl)carbamate (15.0 g, 65.59 mmol) was dissolved in THF (300 mL) and the solution was cooled down to -78 °C. Under stirring, nBuLi (55.1 mL, 2.50 M, 137.7 mmol) was slowly added dropwise over 20 min. The reaction mixture was continued stirring at -78 °C for 30 min to form a pale yellow solution. Subsequently, DMF (15.1 mL, 196.8 mmol) was added dropwise over 5 minutes and stirring was continued at -78 °C for 1 hour. Upon completion of the reaction, the reaction was quenched with MeOH (2 eq.) and subsequently concentrated. After addition of HCl (16 mL), the mixture was concentrated again. The residue was suspended in EtOAc and washed sequentially with 5% NaHCO3 solution and brine before evaporating the solvent. The crude product was suspended in hexane (100 mL) and the precipitate was collected by filtration to afford the target intermediate tert-butyl 4-chloro-3-formylpyridine-2-carbamate (12.8 g, 76% yield) as a white solid.