Sulfuric Acid → HCID 46945201, compound

HRID 1946415Notes

Reaction equation

HRID 1946415 reaction equation
N[C:2]1[CH:3]=[CH:4][C:5]([C:25]([F:28])([F:27])[F:26])=[C:6]([CH2:8][N:9]2[CH:13]=[CH:12][C:11]([NH:14][C:15](=[O:24])[C:16]3[C:21]([F:22])=[CH:20][CH:19]=[CH:18][C:17]=3[F:23])=[N:10]2)[CH:7]=1.S(=O)(=O)(O)O.N([O-])=O.[Na+].[I-:38].[K+]>O>[F:23][C:17]1[CH:18]=[CH:19][CH:20]=[C:21]([F:22])[C:16]=1[C:15]([NH:14][C:11]1[CH:12]=[CH:13][N:9]([CH2:8][C:6]2[CH:7]=[C:2]([I:38])[CH:3]=[CH:4][C:5]=2[C:25]([F:28])([F:27])[F:26])[N:10]=1)=[O:24]

Participants

6

Reactant 4

HCID 1118Sulfuric AcidHCID 4875Potassium IodideHCID 23668193Sodium NitriteHCID 59547994HCID 59547994, compound

Product 1

HCID 46945201HCID 46945201, compound

Reagents, catalysts & solvents 1

HCID 962WaterSolvent2×

Procedure

To a suspension of N-(1-{[5-amino-2-(trifluoromethyl)phenyl]methyl}-1H-pyrazol-3-yl)-2,6-difluorobenzamide (for a preparation see Intermediate 41)(0.6 g, 1.51 mmol) in water (6 ml) in an ice-water bath (internal temperature at 5° C.) was added concentrated sulphuric acid specific gravity 1.84 (1 ml, 18.8 mmol). To the slight suspension was added a solution of sodium nitrite, super free flowing (0.125 g, 1.82 mmol, Aldrich) in water (3 ml) dropwise. The suspension was stirred in an ice-water bath for 20 min. To the mixture was added a solution of potassium iodide, extra pure briquettes (0.377 g, 2.27 mmol, Acros) in ice-cold approximately 1 M sulphuric acid (5.5 ml). The mixture was allowed to warm to ambient temperature and then heated to 80° C. for 30 min under nitrogen. The tarry suspension was partitioned between ethyl acetate (130 ml) and water (50 ml). The phases were separated and the organic phase washed with saturated aqueous sodium hydrogen carbonate (2×50 ml), dried (MgSO4), filtered and the solvent removed at reduced pressure to leave a dark red foam (0.77 g). The sample was loaded in dichloromethane and purified on silica 100 g using 0-100% ethyl acetate-cyclohexane. The appropriate fractions were combined and evaporated in vacuo to give the title compound as a white foam (0.412 g); LCMS: (System 4) MH+=508 tRET=3.10 min.

Workup

  1. custom(internal temperature at 5° C.)
  2. temperatureheated to 80° C. for 30 min under nitrogen
  3. customThe tarry suspension was partitioned between ethyl acetate (130 ml) and water (50 ml)
  4. customThe phases were separated
  5. washthe organic phase washed with saturated aqueous sodium hydrogen carbonate (2×50 ml)
  6. dry with materialdried (MgSO4)
  7. filtrationfiltered
  8. customthe solvent removed at reduced pressure

Sources & evidence

ORD record
ord-83a8edb98c21441b900f6b25e57aefe1
Source dataset
uspto-grants-2013_03
Patent number
US08399436B2

Reaction notes

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