Hydrochloric Acid → HCID 178433880, compound

HRID 386369Notes

Reaction equation

HRID 386369 reaction equation
[NH2:1][C:2]1[C:3]([OH:17])=[C:4]([C:8]2[CH:13]=[CH:12][CH:11]=[C:10]([C:14]([OH:16])=[O:15])[CH:9]=2)[CH:5]=[CH:6][CH:7]=1.Cl.N([O-])=O.[Na+].S(=O)(=O)(O)[NH2:24].[CH3:28][C:29]1[CH:30]=[C:31]([N:36]2[C:40]([OH:41])=[CH:39][C:38]([CH3:42])=[N:37]2)[CH:32]=[CH:33][C:34]=1[CH3:35]>O.C(N(CC)CC)C.CO>[CH3:35][C:34]1[CH:33]=[CH:32][C:31]([N:36]2[N:37]=[C:38]([CH3:42])/[C:39](=[N:24]/[NH:1][C:2]3[CH:7]=[CH:6][CH:5]=[C:4]([C:8]4[CH:13]=[CH:12][CH:11]=[C:10]([C:14]([OH:16])=[O:15])[CH:9]=4)[C:3]=3[OH:17])/[C:40]2=[O:41])=[CH:30][C:29]=1[CH3:28]

Participants

9

Reactant 5

HCID 313Hydrochloric Acid2×HCID 5987Sulfamic AcidHCID 114923323-(3-Amino-2-hydroxyphenyl)benzoic acidHCID 23668193Sodium NitriteHCID 178429255HCID 178429255, compound

Product 1

HCID 178433880HCID 178433880, compound

Reagents, catalysts & solvents 3

HCID 887MethanolSolventHCID 962WaterSolvent2×HCID 8471TriethylamineSolvent

Conditions

Temperature
22 °C

Procedure

Crystalline 3′-amino-2′-hydroxybiphenyl-3-carboxylic acid form II (50 g, 218 mmol, PXRD pattern at FIG. 34) (Supplier: Topharman Shangai Co., Ltd; Batch No: BPCA: 090921BPCA) was added to a solvent mixture of methanol (1 L) and hydrochloric acid, 4 M (137 mL) in a 1 L reactor with stirring at room temperature (cca 22° C.). The resulting solution was stirred for ½ h and then cooled to 0-5° C. A refrigerated solution of sodium nitrite (15 g, 217 mmol) in water (50 mL) was added to the reaction mixture over 20 min (maintaining the reaction temperature below 10° C.) and the stirring was continued for 1 h. A Solution of sulfamic acid (2.22 g, 23 mmol) in water (50 mL) was added to the reaction mixture and stirred for 1 h at 5° C. The resulting reaction mixture was heated to room temperature and triethylamine (cca 80 mL) was added to adjust to pH 7-8. Crystalline 1-(3,4-dimethylphenyl)-3-methyl-1H-pyrazol-5-ol (“pyrazole”) form II (44 g, 218 mmol, PXRD pattern at FIG. 33) (Supplier: Topharman Shangai Co., Ltd; Batch No: 090805PYRAZOL) was added in one portion to the reaction mixture and stirred for 2 h at room temperature, maintaining the pH 7-8. Hydrochloric acid (4 M, cca 40 mL) was added to adjust the pH to 1.8 over 20 minutes with stirring. The precipitated solid was filtered, washed with mixture of MeOH:water (1:1, 60 mL) and dried at 40° C./5 bar for about 18 h to yield 100 g (90%) of EBP as a bright orange powder. PXRD analysis provided the diffractogram as shown in FIG. 20. DSC analysis provided the thermogram as shown in FIG. 21

Workup

  1. stirringThe resulting solution was stirred for ½ h
  2. temperaturecooled to 0-5° C
  3. temperaturemaintaining the reaction temperature below 10° C.) and the stirring
  4. stirringstirred for 1 h at 5° C
  5. customThe resulting reaction mixture
  6. temperaturewas heated to room temperature
  7. stirringstirred for 2 h at room temperature
  8. temperaturemaintaining the pH 7-8
  9. customover 20 minutes
  10. stirringwith stirring
  11. filtrationThe precipitated solid was filtered
  12. washwashed with mixture of MeOH:water (1:1, 60 mL)
  13. customdried at 40° C./5 bar for about 18 h
  14. customto yield 100 g (90%) of EBP as a bright orange powder
  15. customPXRD analysis provided the diffractogram
  16. customDSC analysis provided the thermogram

Sources & evidence

ORD record
ord-d3da9b006d124b59b9f2bb5b141bcc67
Source dataset
uspto-grants-2013_02
Patent number
US08372822B2

Reaction notes

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