Sodium hydride → 2-(1-(2,2-dimethoxyethyl)-1H-indazol-5-yloxy)-5-fluorobenzonitrile

HRID 1897512Notes

Reaction equation

HRID 1897512 reaction equation
[F:1][C:2]1[CH:3]=[CH:4][C:5]([O:10][C:11]2[CH:12]=[C:13]3[C:17](=[CH:18][CH:19]=2)[NH:16][N:15]=[CH:14]3)=[C:6]([CH:9]=1)[C:7]#[N:8].Br[CH2:21][CH:22]([O:25][CH3:26])[O:23][CH3:24].[H-].[Na+]>CN(C=O)C.[I-].C([N+](CCCC)(CCCC)CCCC)CCC.O>[CH3:24][O:23][CH:22]([O:25][CH3:26])[CH2:21][N:16]1[C:17]2[C:13](=[CH:12][C:11]([O:10][C:5]3[CH:4]=[CH:3][C:2]([F:1])=[CH:9][C:6]=3[C:7]#[N:8])=[CH:19][CH:18]=2)[CH:14]=[N:15]1

Participants

7

Reactant 3

HCID 24758Sodium hydrideHCID 816722-Bromo-1,1-dimethoxyethaneHCID 57418753HCID 57418753, compound

Product 1

HCID 666711532-(1-(2,2-dimethoxyethyl)-1H-indazol-5-yloxy)-5-fluorobenzonitrileYield 49%

Reagents, catalysts & solvents 3

HCID 67553Tetrabutylammonium IodideCatalystHCID 962WaterSolventHCID 6228DimethylformamideSolvent

Procedure

To a cooled (0° C.) solution of 5-fluoro-2-(1H-indazol-5-yloxy)-benzonitrile (0.100 g, 0.395 mmol) and 2-bromo-1,1-dimethoxyethane (0.114 g, 0.671 mmol) in DMF (4 mL) was added NaH (0.024 g of 60%, 0.59 mmol). The reaction mixture was warmed to room temperature and stirred for 1 hour. Tetrabutyl ammonium iodide (0.029 g, 0.079 mmol) was added to the mixture and it was heated to 60° C. for 3 hours. The mixture was cooled to room temperature, diluted with water (4 mL), and extracted with ether (3×30 mL). The combined extracts were washed with water (2×5 mL) and brine, dried over MgSO4, and concentrated under reduced pressure. The residue was chromatographed eluting with ethyl acetate/hexanes (1:2) to afford 0.066 g of product (49% yield).

Workup

  1. temperaturewas heated to 60° C. for 3 hours
  2. temperatureThe mixture was cooled to room temperature
  3. extractionextracted with ether (3×30 mL)
  4. washThe combined extracts were washed with water (2×5 mL) and brine
  5. dry with materialdried over MgSO4
  6. concentrationconcentrated under reduced pressure
  7. customThe residue was chromatographed
  8. washeluting with ethyl acetate/hexanes (1:2)

Sources & evidence

ORD record
ord-66e7f202f2234a23b7418591f6d1f440
Source dataset
uspto-grants-2013_08
Patent number
US08518983B2

Reaction notes

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