Potassium Hydroxide → tert-butyl 5-(difluoromethoxy)-3-iodo-1H-indazole-1-carboxylate

HRID 246720

Reaction equation

HRID 246720 reaction equation
Br[C:2](P(=O)(OCC)OCC)([F:4])[F:3].[OH:13][C:14]1[CH:15]=[C:16]2[C:20](=[CH:21][CH:22]=1)[N:19]([C:23]([O:25][C:26]([CH3:29])([CH3:28])[CH3:27])=[O:24])[N:18]=[C:17]2[I:30].[OH-].[K+]>CC#N.O.CCOC(C)=O>[F:3][CH:2]([F:4])[O:13][C:14]1[CH:15]=[C:16]2[C:20](=[CH:21][CH:22]=1)[N:19]([C:23]([O:25][C:26]([CH3:27])([CH3:29])[CH3:28])=[O:24])[N:18]=[C:17]2[I:30]

Participants

6

Reactant 3

HCID 14797Potassium HydroxideHCID 144101Bromodifluoromethyl diethylphosphonateHCID 71280823tert-Butyl 5-hydroxy-3-iodo-1H-indazole-1-carboxylate

Product 1

HCID 71279601tert-butyl 5-(difluoromethoxy)-3-iodo-1H-indazole-1-carboxylateYield 47%

Reagents, catalysts & solvents 2

HCID 8857Ethyl AcetateSolventHCID 18373917Acetonitrile--water (1/1)Solvent

Procedure

Diethyl bromodifluoromethylphosphonate (1.13 g, 4.22 mmol) was added in one portion to a cooled (−30° C.) solution of tert-butyl 5-hydroxy-3-iodo-1H-indazole-1-carboxylate and KOH (2.36 g, 42.2 mmol) in MeCN/H2O (20 mL/20 mL). The reaction mixture was allowed to warm to room temperature. After 20 min, the reaction mixture was diluted with EtOAc (15 mL), and the organic phase was separated. The water phase was extracted with EtOAc (10 mL). The combined organic layers were dried over Na2SO4. Evaporation of the solvent gave a crude product that was purified by column chromatography on silica gel eluting with petroleum ether/EtOAc (5:1) to give tert-butyl 5-(difluoromethoxy)-3-iodo-1H-indazole-1-carboxylate (0.41 g, 47% over two steps) as a white solid. 1H NMR (300 MHz, CDCl3): δ 8.13 (d, 1H, J=9.0 Hz), 7.39 (dd, 1H, J=9, 2.4 Hz), 7.23 (d, 1H, J=2.4 Hz), 6.57 (t, 1H, J=73.2 Hz), 1.73 (s, 9H).

Workup

  1. customthe organic phase was separated
  2. extractionThe water phase was extracted with EtOAc (10 mL)
  3. dry with materialThe combined organic layers were dried over Na2SO4
  4. customEvaporation of the solvent
  5. customgave a crude product that
  6. customwas purified by column chromatography on silica gel eluting with petroleum ether/EtOAc (5:1)

Sources & evidence

ORD record
ord-f47ff4e00fbd4e3f93922ff290baba21
Source dataset
uspto-grants-2014_02
Patent number
US08658646B2

Linked notes

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