Sulfuric Acid → HCID 135800031, compound

HRID 1464577Notes

Reaction equation

HRID 1464577 reaction equation
N[C:2]1[CH:10]=[C:9]2[C:5]([C:6]([Cl:17])=[N:7][N:8]2[CH2:11][C:12]([O:14][CH2:15][CH3:16])=[O:13])=[CH:4][CH:3]=1.S(=O)(=O)(O)[OH:19].N([O-])=O.[Na+]>O>[Cl:17][C:6]1[C:5]2[C:9](=[CH:10][C:2]([OH:19])=[CH:3][CH:4]=2)[N:8]([CH2:11][C:12]([O:14][CH2:15][CH3:16])=[O:13])[N:7]=1

Participants

5

Reactant 3

HCID 1118Sulfuric AcidHCID 19086725HCID 19086725, compoundHCID 23668193Sodium Nitrite

Product 1

HCID 135800031HCID 135800031, compound

Reagents, catalysts & solvents 1

HCID 962WaterSolvent2×

Conditions

Temperature
-5 °C

Procedure

Ethyl 6-amino-3-chloroindazol-1-ylacetate (11.5 g) was warmed with 35% sulphuric acid to obtain a solution. Ice (54 g) was added and the solution cooled to -5° C. in an ice/salt bath. A solution of sodium nitrite (4 g) in water (43cm3) was added slowly with stirring and cooling at 0° C. When addition was complete, the mixture was stirred for 15 minutes at 0° C. A pre-cooled solution (5° C.) of cupric nitrate (173 g) in water (1.6L) was added with stirring and cooling at 5° C. Cooper (I) oxide (6.5 g) was added and the mixture stirred at 0° C. for 0.5 hours, after which it was allowed to warm to room temperature for 4.5 hours. The reaction mixture was extracted with ethyl acetate (×4) and the combined organic phase washed with water, dried (MgSO4), filtered and the solvent removed from the filtrate under vacuum. The residue was stirred with ethanol (400cm3) saturated with hydrogen chloride overnight, evaporated under vacuum and then partitioned between water and ethyl acetate. The organic phase was washed with water, dried (MgSO4), filtered and the solvent removed from the filtrate under vacuum. The residue was purified by flash chromatography (SiO2 ; chloroform:ether,3:2) to give ethyl 3-chloro-6-hydroxyindazol-1-ylacetate (4.34 g) as a brown solid; recrystallised from toluene, m.pt 138°-142° C.

Workup

  1. customto obtain a solution
  2. temperaturecooling at 0° C
  3. additionWhen addition
  4. stirringthe mixture was stirred for 15 minutes at 0° C
  5. stirringwith stirring
  6. temperaturecooling at 5° C
  7. stirringthe mixture stirred at 0° C. for 0.5 hours
  8. temperatureto warm to room temperature for 4.5 hours
  9. extractionThe reaction mixture was extracted with ethyl acetate (×4)
  10. washthe combined organic phase washed with water
  11. dry with materialdried (MgSO4)
  12. filtrationfiltered
  13. customthe solvent removed from the filtrate under vacuum
  14. stirringThe residue was stirred with ethanol (400cm3) saturated with hydrogen chloride overnight
  15. customevaporated under vacuum
  16. custompartitioned between water and ethyl acetate
  17. washThe organic phase was washed with water
  18. dry with materialdried (MgSO4)
  19. filtrationfiltered
  20. customthe solvent removed from the filtrate under vacuum
  21. customThe residue was purified by flash chromatography (SiO2 ; chloroform:ether,3:2)

Sources & evidence

ORD record
ord-efcba13dbfda4f21bc52b40a59dc70be
Source dataset
uspto-grants-1994_04
Patent number
US05306692

Reaction notes

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