Phosphorus oxychloride → 4-Chloro-3-nitro-1,5-naphthyridine

Participants

Reaction Conditions

Reaction Steps

Under a nitrogen atmosphere, a suspension of 3-nitro[1,5]naphthyridin-4-ol (12.00 kg, 67.78 mol) in DMF (49 L) was stirred for 30 minutes at a temperature of 20° C. to 24° C. Phosphorous oxychloride (10.6 kg, 69.1 mol) was added slowly over a period of 53 minutes while maintaining the temperature at 20.6° C. to 25.6° C. Additional DMF (5 L) was used to rinse the addition vessel and added to the reaction. The reaction was stirred for 19 hours and 17 minutes at a temperature of 20° C. to 24° C. and then added quickly, over a period of four minutes, to purified water (275 L) that had been cooled to 8.4° C. During the addition, the temperature of the mixture did not exceed 18° C. Additional water (80 L) was used to rinse the original vessel and added quickly to the resulting mixture, which ranged in temperature from 16.6° C. to 17.2° C. during this addition. The mixture resulting from the additions was stirred for 30 minutes while cooling to a temperature of approximately 10° C. A solid formed and was isolated by filtration and washed with cold water (6×33 L at 10° C.) to provide 20.55 kg of 4-chloro-3-nitro[1,5]naphthyridine, which contained some water and was used in Part B within 2.75 hours of filtration.

Provenance & Evidence