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

HRID 2090170Notes

Reaction equation

HRID 2090170 reaction equation
[N+:1]([C:4]1[CH:5]=[N:6][C:7]2[C:12]([C:13]=1O)=[N:11][CH:10]=[CH:9][CH:8]=2)([O-:3])=[O:2].P(Cl)(Cl)([Cl:17])=O>CN(C=O)C>[Cl:17][C:13]1[C:12]2[C:7](=[CH:8][CH:9]=[CH:10][N:11]=2)[N:6]=[CH:5][C:4]=1[N+:1]([O-:3])=[O:2]

Participants

4

Reactant 2

HCID 24813Phosphorus oxychlorideHCID 178526774HCID 178526774, compound

Product 1

HCID 131227874-Chloro-3-nitro-1,5-naphthyridineYield 144.7%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent2×

Conditions

Temperature
8.399999618530273 °C

Procedure

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.

Workup

  1. temperaturewhile maintaining the temperature at 20.6° C. to 25.6° C
  2. washto rinse the addition vessel
  3. additionadded to the reaction
  4. stirringThe reaction was stirred for 19 hours and 17 minutes at a temperature of 20° C. to 24° C.
  5. additionadded quickly, over a period of four minutes
  6. customto purified water (275 L) that
  7. additionDuring the addition
  8. customdid not exceed 18° C
  9. washto rinse the original vessel
  10. additionadded quickly to the resulting mixture, which
  11. additionranged in temperature from 16.6° C. to 17.2° C. during this addition
  12. customThe mixture resulting from the additions
  13. stirringwas stirred for 30 minutes
  14. temperaturewhile cooling to a temperature of approximately 10° C
  15. customA solid formed
  16. customwas isolated by filtration
  17. washwashed with cold water (6×33 L at 10° C.)

Sources & evidence

ORD record
ord-db3dd0114ce84bd0a43de9b7070abd5a
Source dataset
uspto-grants-2013_05
Patent number
US08436176B2

Reaction notes

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