Cesium carbonate → 5-(2,4-Difluorophenoxy)-1-isobutyl-6-oxiranylmethoxy-1H-indazole

HRID 1897476Notes

Reaction equation

HRID 1897476 reaction equation
[F:1][C:2]1[CH:22]=[C:21]([F:23])[CH:20]=[CH:19][C:3]=1[O:4][C:5]1[CH:6]=[C:7]2[C:11](=[CH:12][C:13]=1[OH:14])[N:10]([CH2:15][CH:16]([CH3:18])[CH3:17])[N:9]=[CH:8]2.C([O-])([O-])=O.[Cs+].[Cs+].Br[CH2:31][CH:32]1[CH2:34][O:33]1>CC(N(C)C)=O.CCOCC.O>[F:1][C:2]1[CH:22]=[C:21]([F:23])[CH:20]=[CH:19][C:3]=1[O:4][C:5]1[CH:6]=[C:7]2[C:11](=[CH:12][C:13]=1[O:14][CH2:31][CH:32]1[CH2:34][O:33]1)[N:10]([CH2:15][CH:16]([CH3:18])[CH3:17])[N:9]=[CH:8]2

Participants

7

Reactant 3

HCID 10796Cesium carbonateHCID 18430EpibromohydrinHCID 1361636625-(2,4-difluorophenoxy)-1-isobutyl-1H-indazol-6-ol

Product 1

HCID 865944235-(2,4-Difluorophenoxy)-1-isobutyl-6-oxiranylmethoxy-1H-indazoleYield 77%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 3283Diethyl EtherSolventHCID 31374DimethylacetamideSolvent

Procedure

To a solution of 5-(2,4-difluorophenoxy)-1-isobutyl-1H-indazol-6-ol (0.15 g, 0.47 mmol) in DMA (5 mL) was added Cs2CO3 (0.46 g, 1.41 mmol). After stirring the mixture for 3 hours, 2-bromomethyloxirane (0.13 g, 0.94 mmol) was added and the resulting mixture was stirred at room temperature for 16 hours. The mixture was diluted with ether and water and the layers were separated. The aqueous layer was extracted with ether (3×) and the combined organic layers were washed with water and brine, and dried over Na2SO4. The crude product was concentrated under reduced pressure and used in the next reaction without further purification (0.135 g, 77% yield).

Workup

  1. stirringthe resulting mixture was stirred at room temperature for 16 hours
  2. customthe layers were separated
  3. extractionThe aqueous layer was extracted with ether (3×)
  4. washthe combined organic layers were washed with water and brine
  5. dry with materialdried over Na2SO4
  6. concentrationThe crude product was concentrated under reduced pressure
  7. customused in the next reaction without further purification (0.135 g, 77% yield)

Sources & evidence

ORD record
ord-83fb2424482a4af7bf9fc2a6cbf730ee
Source dataset
uspto-grants-2013_08
Patent number
US08518983B2

Reaction notes

Loading…