Nitric Acid → HCID 178498157, compound

HRID 241536Notes

Reaction equation

HRID 241536 reaction equation
[NH2:1][C:2]1[CH:11]=[CH:10][C:5]([C:6]([O:8][CH3:9])=[O:7])=[C:4]([O:12][CH3:13])[CH:3]=1.[N:14]#[C:15][NH2:16].[N+:17]([O-:20])([OH:19])=[O:18]>CO>[N+:17]([O-:20])([OH:19])=[O:18].[NH2:16][C:15]([NH:1][C:2]1[CH:11]=[CH:10][C:5]([C:6]([O:8][CH3:9])=[O:7])=[C:4]([O:12][CH3:13])[CH:3]=1)=[NH:14]

Participants

5

Reactant 3

HCID 944Nitric AcidHCID 9864CyanamideHCID 168705Methyl 4-amino-o-anisate

Product 1

HCID 178498157HCID 178498157, compoundYield 50%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent2×

Conditions

Temperature
27.5 °C

Procedure

Into a reactor at room temperature was added methyl 4-amino-2-methoxybenzoate (4, 38 kg, 210 mol) and methanol (224 L). The mixture was stirred at 25 to 30° C. for 30 min. Aqueous cyanamide (50% w/w, 43 kg, 512 mol) was added over a minimum of 30min at 20 to 25° C. The reaction mixture was heated to reflux using a maximum jacket temperature of 75° C. Concentrated nitric acid (45 kg, 499 mol) was added over a minimum of 60 min. The resulting mixture was heated at reflux for 2 h. A suspension of seed crystals (16 g in 600 mL methanol) was added and the mixture was stirred using a 75° C. jacket temperature for 60 to 90 min. The mixture was cooled to 20 to 25° C. over at least 2 h and stirred for an additional 2 h. The mixture was filtered and washed with methanol (180 L) while stirring for 1 h. The wet cake was washed a second time with methanol (180 L) while stirring for 1 h. The resulting wet cake was dried under vacuum at 25° C. to provide 30.0 kg (50% yield) of 5. 1H NMR (300 MHz, DMSO-d6) δ 9.82 (s, 1H), 7.70 (d, J=8.2 Hz, 1H), 7.57 (s, 4H), 6.97 (d, J=2.3 Hz, 1H), 6.84 (dd, J=2.3, 8.2 Hz, 1H), 3.81 (s, 3H), 3.76 (s, 3H); MS (ESI) m/z 224.4 (M+, 100%).

Workup

  1. temperatureThe reaction mixture was heated
  2. temperatureto reflux
  3. customa maximum jacket temperature of 75° C
  4. temperatureThe resulting mixture was heated
  5. temperatureat reflux for 2 h
  6. additionwas added
  7. stirringthe mixture was stirred
  8. customusing a 75° C.
  9. customfor 60 to 90 min
  10. temperatureThe mixture was cooled to 20 to 25° C. over at least 2 h
  11. stirringstirred for an additional 2 h
  12. filtrationThe mixture was filtered
  13. washwashed with methanol (180 L)
  14. stirringwhile stirring for 1 h
  15. washThe wet cake was washed a second time with methanol (180 L)
  16. stirringwhile stirring for 1 h
  17. customThe resulting wet cake was dried under vacuum at 25° C.

Sources & evidence

ORD record
ord-00171f540a89434391489819e9e5503a
Source dataset
uspto-grants-2014_02
Patent number
US08653064B2

Reaction notes

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