2,5-difluoro-N-methylaniline

Conditions: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To 6,7-dihydro-3,7-dimethyl-4-hydroxy-6-oxo-thieno[2,3-b]pyridine-5-carboxylic acid (4.18. mmol, 1.0 g) in dichloromethane (10 ml), triethylamine (4 equiv., 16.7 mmol, 2.4 ml) and N-methyl-2,5-difluoroaniline (1.2 equiv., 5.0 mmol, 720 mg) were added. To the mixture stirred under nitrogen and cooled to 0° C., a solution of thionyl chloride (1.3 equiv., 5.4 mmol, 0.4 ml) in dichloromethane (5 ml) then was added during 30 min. The stirring was continued at 0° C. for 1 h and then at room temperature for another 20 min. The reaction mixture was diluted with chloroform and quickly washed with cold 1M sulphuric acid. The organic phase then was immediately extracted with 0.5 M NaOH. Remaining traces of chlorinated organic solvents were removed using a rotary evaporator. The pH was adjusted to just above the point where the desired product starts to precipitate (approximately pH 6.5) and the solution was filtered through celite. The product was precipitated by acidification with 1 M HCl until pH was approximately 1-2 and the mixture was allowed to stand for 2 hrs. The resulting precipitate was collected by filtration, washed with water, and dried under reduced pressure to give the title compound (1.26 g, 83%). at room temperature for another 20 min quickly washed with cold 1M sulphuric acid The organic phase then was immediately extracted with 0.5 M NaOH Remaining traces of chlorinated organic solvents were removed a rotary evaporator to precipitate (approximately pH 6.5) and the solution was filtered through celite The product was precipitated by acidification with 1 M HCl until pH was approximately 1-2 to stand for 2 hrs The resulting precipitate was collected by filtration washed with water dried under reduced pressure