Methanol → 6-bromo-5-(2-fluoro-4-nitrophenoxy)-1H-indazole

HRID 1662008Notes

Reaction equation

HRID 1662008 reaction equation
[Br:1][C:2]1[C:3]([O:17][C:18]2[CH:23]=[CH:22][C:21]([N+:24]([O-:26])=[O:25])=[CH:20][C:19]=2[F:27])=[CH:4][C:5]2[C:9]([CH:10]=1)=[N:8][N:7](C1CCCCO1)[CH:6]=2.CO.CS(O)(=O)=O.[OH-].[Na+]>C(Cl)Cl.O>[Br:1][C:2]1[CH:10]=[C:9]2[C:5]([CH:6]=[N:7][NH:8]2)=[CH:4][C:3]=1[O:17][C:18]1[CH:23]=[CH:22][C:21]([N+:24]([O-:26])=[O:25])=[CH:20][C:19]=1[F:27]

Participants

7

Reactant 4

HCID 887MethanolHCID 6395Methanesulfonic AcidHCID 14798Sodium HydroxideHCID 667671846-Bromo-5-(2-fluoro-4-nitrophenoxy)-2-(tetrahydro-2H-pyran-2-yl)-2H-indazole

Product 1

HCID 667671536-bromo-5-(2-fluoro-4-nitrophenoxy)-1H-indazoleYield 96.9%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6344DichloromethaneSolvent

Conditions

Temperature
50 °C

Procedure

To a 3000 mL flask is added 6-bromo-5-(2-fluoro-4-nitrophenoxy)-2-(tetrahydro-2H-pyran-2-yl)-2H-indazole (250 g, 573.1 mmol) followed by MeOH (1000 mL) and MeSO3H (1 12.71 mL,1.72 mol) and heated to 50° C. for 14 hours. Solid crystallizes out of solution. The mixture is then cooled to RT. The reaction mixture is concentrated under vacuum at 45° C. to dryness to get solid. The solid is diluted with DCM (2000 mL) and treated with water (1000 mL) and 5N NaOH (about 350 mL) until the pH is 8-9. The organic layer is separated and the solvent is removed followed by azeotrope with toluene to give 195.6 g of the yellow solid material. MS (m/z): 354.0 (M+H).

Workup

  1. customSolid crystallizes out of solution
  2. temperatureThe mixture is then cooled to RT
  3. concentrationThe reaction mixture is concentrated under vacuum at 45° C. to dryness
  4. customto get solid
  5. customThe organic layer is separated
  6. customthe solvent is removed

Sources & evidence

ORD record
ord-3a652f6793d541bebb946c0308409e74
Source dataset
uspto-grants-2011_10
Patent number
US08030302B2

Reaction notes

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