Hydrochloric Acid → 3-Chloro-2-(4-chloro-5-(difluoromethoxy)-2-fluorophenyl)-4,5,6,7-tetrahydroindazole

HRID 2309314Notes

Reaction equation

HRID 2309314 reaction equation
[OH-].[Na+].[Cl:3][C:4]1[N:5]([C:13]2[CH:18]=[C:17]([OH:19])[C:16]([Cl:20])=[CH:15][C:14]=2[F:21])[N:6]=[C:7]2[C:12]=1[CH2:11][CH2:10][CH2:9][CH2:8]2.Cl[CH:23]([F:25])[F:24].Cl>O.C(O)(C)C>[Cl:3][C:4]1[N:5]([C:13]2[CH:18]=[C:17]([O:19][CH:23]([F:25])[F:24])[C:16]([Cl:20])=[CH:15][C:14]=2[F:21])[N:6]=[C:7]2[C:12]=1[CH2:11][CH2:10][CH2:9][CH2:8]2

Participants

7

Reactant 4

HCID 313Hydrochloric AcidHCID 6372ChlorodifluoromethaneHCID 14798Sodium Hydroxide2×HCID 1850782-Chloro-5-(3-chloro-4,5,6,7-tetrahydroindazol-2-yl)-4-fluorophenol

Product 1

HCID 1847643-Chloro-2-(4-chloro-5-(difluoromethoxy)-2-fluorophenyl)-4,5,6,7-tetrahydroindazole

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 3776IsopropanolSolvent

Procedure

To a solution of 36 ml of isopropanol, 21 ml of water and 6.0 ml of sodium hydroxide was added 5.28 g of 3-chloro-2-(4-chloro-2-fluoro-5-hydroxyphenyl)-4,5,6,7-tetrahydro-2H-indazole II-2, and the resultant mixture was heated at 50° to 60° C. to give a solution. Excessive chlorodifluoromethane gas was introduced, and each 4.5 g of 50% aqueous sodium hydroxide was added 1.5 and 3 hours after starting the gas inlet and further said gas inlet was continued for additional one hour. After cooling, the reaction mixture was neutralized with 2N hydrochloric acid and extracted with dichloromethane. The organic layer was dried and concentrated. The residue was chromatographed on a column of silica gel, eluting with n-hexane-ethyl acetate (4:1 v/v). The eluate was concentrated to give 5.24 g of the titled compound I-2.

Workup

  1. customto give a solution
  2. temperatureAfter cooling
  3. extractionextracted with dichloromethane
  4. customThe organic layer was dried
  5. concentrationconcentrated
  6. customThe residue was chromatographed on a column of silica gel
  7. washeluting with n-hexane-ethyl acetate (4:1 v/v)
  8. concentrationThe eluate was concentrated

Sources & evidence

ORD record
ord-1d8b6eb5ec0c4208819f309b6ff85946
Source dataset
uspto-grants-1987_09
Patent number
US04695312

Reaction notes

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