Water → 6-Bromo-5-(2-fluoro-4-nitrophenoxy)-2-(tetrahydro-2H-pyran-2-yl)-2H-indazole

HRID 1661977Notes

Reaction equation

HRID 1661977 reaction equation
[Br:1][C:2]1[C:3]([OH:17])=[CH:4][C:5]2[C:9]([CH:10]=1)=[N:8][N:7]([CH:11]1[CH2:16][CH2:15][CH2:14][CH2:13][O:12]1)[CH:6]=2.[F:18][C:19]1[CH:20]=[C:21]([N+:26]([O-:28])=[O:27])[CH:22]=[CH:23][C:24]=1F.C([O-])(O)=O.[Na+].O>CN(C=O)C>[Br:1][C:2]1[C:3]([O:17][C:24]2[CH:23]=[CH:22][C:21]([N+:26]([O-:28])=[O:27])=[CH:20][C:19]=2[F:18])=[CH:4][C:5]2[C:9]([CH:10]=1)=[N:8][N:7]([CH:11]1[CH2:16][CH2:15][CH2:14][CH2:13][O:12]1)[CH:6]=2

Participants

6

Reactant 4

HCID 962WaterHCID 1230531,2-Difluoro-4-nitrobenzeneHCID 516892Sodium BicarbonateHCID 667670386-Bromo-2-(tetrahydro-2H-pyran-2-yl)-2H-indazol-5-ol

Product 1

HCID 667671846-Bromo-5-(2-fluoro-4-nitrophenoxy)-2-(tetrahydro-2H-pyran-2-yl)-2H-indazoleYield 64.9%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
70 °C

Procedure

To a solution of 6-bromo-2-(tetrahydro-2H-pyran-2-yl)-2H-indazol-5-ol (1.475 kg, 4.96 mol) in DMF (5.3 L) is added 3,4-difluoronitrobenzene (1.18 kg, 7.45 mol) and NaHCO3 (625.5 g, 7.45 mol) at RT. The reaction mixture is heated at 70° C. for 10 hours and then cooled to less than 20° C. Deionized (DI) water (7.9 L) is slowly added to the solution and the resulting slurry is stirred at 15° C. for one hour. The solid is collected by vacuum filtration, and the solid cake is washed with water (8 L). It is then air dried under vacuum on filter and is triturated with methyl MTBE (18.6 L) at reflux conditions for two hours. The slurry is then cooled to RT and the solid is collected by vacuum filtration. The solid cake is washed with MTBE (4 L×2) and dried in a vacuum oven at 35° C. to give the desired product (1.405 kg, 64.9% yield). MS (m/z): 436.0 (M+H).

Workup

  1. temperaturecooled to less than 20° C
  2. filtrationThe solid is collected by vacuum filtration
  3. washthe solid cake is washed with water (8 L)
  4. customair dried under vacuum
  5. filtrationon filter
  6. customis triturated with methyl MTBE (18.6 L)
  7. temperatureat reflux conditions for two hours
  8. temperatureThe slurry is then cooled to RT
  9. filtrationthe solid is collected by vacuum filtration
  10. washThe solid cake is washed with MTBE (4 L×2)
  11. customdried in a vacuum oven at 35° C.

Sources & evidence

ORD record
ord-7e0e20375b0f4bd5806d8e47f521edf4
Source dataset
uspto-grants-2011_10
Patent number
US08030302B2

Reaction notes

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