Phosphorus oxychloride → 4-Chloro-3-nitro-1,2-dihydropyridin-2-one

HRID 1857041Notes

Reaction equation

HRID 1857041 reaction equation
[OH:1][C:2]1[C:7]([N+:8]([O-:10])=[O:9])=[C:6](O)[CH:5]=[CH:4][N:3]=1.P(Cl)(Cl)([Cl:14])=O.C(N(CC)C(C)C)(C)C>C1(C)C=CC=CC=1>[Cl:14][C:6]1[CH:5]=[CH:4][NH:3][C:2](=[O:1])[C:7]=1[N+:8]([O-:10])=[O:9]

Participants

5

Reactant 3

HCID 24813Phosphorus oxychloride5×HCID 81531Diisopropylethylamine5×HCID 178526878HCID 178526878, compound2×

Product 1

HCID 5192824-Chloro-3-nitro-1,2-dihydropyridin-2-one

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent

Conditions

Temperature
47 °C

Procedure

A 150 mL flask is charged with 2,4-dihydroxy-3-nitropyridine (Compound XII) (10.0 g, 0.064 mole), and toluene (30 mL). The mixture is stirred at moderate speed and warmed to 47° C. Phosphorus oxychloride (POCl3) (4.4 g, 0.0289 moles) is added over 10 minutes, via a syringe pump, giving an exotherm to 49° C. N,N-diisopropylethylamine (DIPEA) (2.22 g, 0.017 moles) is added over 10 minutes, giving an exotherm to 51° C. Another portion of POCl3 (4.4 g, 0.0289 moles) is added over 10 minutes, followed by another portion of DIPEA (2.22 g, 0.017 moles) over 10 minutes. A third portion of POCl3 (4.4 g, 0.0289 moles) is added over 10 minutes, followed by a third portion of DIPEA (2.22 g, 0.017 moles) over 10 minutes, followed by a final portion of POCl3 (4.4 g, 0.0289 moles) over 10 minutes (total POCl3 added is 17.7 g), then by a final portion of DIPEA (2.22 g, 0.017 moles) over 10 min. (total DIPEA added is 8.9 g). The reaction is then stirred at 50° C. for 5 hr until IPC indicates complete consumption of Compound XII. The reaction is allowed to cool to 20° C. over 30 minutes and 50 mL of water is added over 1.5 hr allowing the temperature to rise to 47° C. This mixture is stirred for four hours while cooling to 25° C. The batch is filtered washing twice with 15 mL of water, then twice with 15 mL of toluene. The product is dried to give Compound II.

Workup

  1. customgiving an exotherm to 49° C
  2. customgiving an exotherm to 51° C
  3. customover 10 minutes
  4. stirringThe reaction is then stirred at 50° C. for 5 hr until IPC
  5. customconsumption of Compound XII
  6. temperatureto cool to 20° C. over 30 minutes
  7. addition50 mL of water is added over 1.5 hr
  8. customto rise to 47° C
  9. stirringThis mixture is stirred for four hours
  10. temperaturewhile cooling to 25° C
  11. filtrationThe batch is filtered
  12. washwashing twice with 15 mL of water
  13. customThe product is dried

Sources & evidence

ORD record
ord-60923495833e4985b6e1784bb712b46f
Source dataset
uspto-grants-2000_11
Patent number
US06143894

Reaction notes

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