Iodine → HCID 178506407, compound

HRID 246374Notes

Reaction equation

HRID 246374 reaction equation
[F:1][CH:2]([F:16])[O:3][C:4]1[CH:5]=[C:6]2[C:10](=[CH:11][CH:12]=1)[NH:9][N:8]=[C:7]2C(O)=O.C(=O)(O)[O-].[Na+].[I-:22].[Na+].II>ClC(Cl)C.O.ClCCl>[F:1][CH:2]([F:16])[O:3][C:4]1[CH:5]=[C:6]2[C:10](=[CH:11][CH:12]=1)[NH:9][N:8]=[C:7]2[I:22]

Participants

8

Reactant 4

HCID 807IodineHCID 5238Sodium IodideHCID 516892Sodium BicarbonateHCID 534150555-(Difluoromethoxy)-1H-indazole-3-carboxylic acid

Product 1

HCID 178506407HCID 178506407, compoundYield 84.3%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 6344DichloromethaneSolventHCID 63651,1-DichloroethaneSolvent

Conditions

Temperature
100 °C

Procedure

To a mixture of 5-(difluoromethoxy)-1H-indazole-3-carboxylic acid (1 g, 4.38 mmol), and sodium bicarbonate (1.22 g, 563 μL, 14.5 mmol) in dichloroethane (10.0 mL) and water (10.0 mL) were added in one portion sodium iodide (1.71 g, 11.4 mmol) and iodine (1.45 g, 5.7 mmol) and the mixture heated at to 100° C. (oil bath temperature) with vigorous stirring for 45 minutes. After cooling to 25° C. the mixture was diluted with dichloromethane then washed with 10% Na2S2O3 and saturated NaHCO3. The organic phases were combined, dried (MgSO4) and concentrated to an off-white solid which was dissolved in dichloromethane, hexane added to promote solid formation and allowed to stand. The solid formed was separated by decanting the mother liquor and dried to give 5-(difluoromethoxy)-3-iodo-1H-indazole (1145 mg, 3.69 mmol, 84.3%) as a white fluffy solid. MS (M−H)−=308.9; 1H NMR (CDCl3) δ: 7.52 (d, J=9.1 Hz, 1H), 7.28-7.36 (m, 1H), 6.57 (t, J=73.7 Hz, 1H).

Workup

  1. temperatureAfter cooling to 25° C. the mixture
  2. washthen washed with 10% Na2S2O3 and saturated NaHCO3
  3. dry with materialdried (MgSO4)
  4. concentrationconcentrated to an off-white solid which
  5. dissolutionwas dissolved in dichloromethane
  6. additionhexane added
  7. customThe solid formed
  8. customwas separated
  9. customby decanting the mother liquor
  10. customdried

Sources & evidence

ORD record
ord-e76a6054f6ca422f84190ac15e1ecfb1
Source dataset
uspto-grants-2014_02
Patent number
US08658646B2

Reaction notes

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