Sodium hydride → 2-Bromo-4-(6,6-dimethyl-4-oxo-3-difluoromethyl-4,5,6,7-tetrahydroindazol-1-yl)-benzonitrile

HRID 602403Notes

Reaction equation

HRID 602403 reaction equation
[H-].[Na+].[F:3][CH:4]([F:17])[C:5]1[C:13]2[C:12](=[O:14])[CH2:11][C:10]([CH3:16])([CH3:15])[CH2:9][C:8]=2[NH:7][N:6]=1.[Br:18][C:19]1[CH:26]=[C:25](F)[CH:24]=[CH:23][C:20]=1[C:21]#[N:22]>CS(C)=O.[NH4+].[Cl-].O>[Br:18][C:19]1[CH:26]=[C:25]([N:7]2[C:8]3[CH2:9][C:10]([CH3:15])([CH3:16])[CH2:11][C:12](=[O:14])[C:13]=3[C:5]([CH:4]([F:3])[F:17])=[N:6]2)[CH:24]=[CH:23][C:20]=1[C:21]#[N:22]

Participants

7

Reactant 3

HCID 24758Sodium hydrideHCID 1189392-Bromo-4-fluorobenzonitrileHCID 441903493-Difluoromethyl-6,6-dimethyl-1,5,6,7-tetrahydro-indazol-4-one

Product 1

HCID 118546862-Bromo-4-(6,6-dimethyl-4-oxo-3-difluoromethyl-4,5,6,7-tetrahydroindazol-1-yl)-benzonitrileYield 49.2%

Reagents, catalysts & solvents 3

HCID 679Dimethyl SulfoxideSolventHCID 962WaterSolventHCID 25517Ammonium ChlorideSolvent

Procedure

NaH (350 mg) was added to a solution of 3-difluoromethyl-6,6-dimethyl-1,5,6,7-tetrahydro-indazol-4-one (3.12 g) in DMSO (75 mL) at room temperature. After 20 minutes of stirring, 2-bromo-4-fluorobenzonitrile (4.67 g) was added and stirred at 45° C. overnight. The reaction was diluted with saturated aqueous NH4Cl (100 mL), H2O (100 mL). The mixture was extracted with ethyl acetate (4×150 mL), dried over Na2SO4, filtered, concentrated, purified by column chromatography eluting with a 1:2 mixture of ethyl acetate/hexanes. The concentrate of desired fractions was made into a slurry in ether, stirred for 2 h, filtered, washed by hexane to give pure solid 2-bromo-4-(6,6-dimethyl-4-oxo-3-difluoromethyl-4,5,6,7-tetrahydro-indazol-1-yl)-benzonitrile (2.82 g, 49.2%). LCMS m/z: (M+H)=395.65, (MW: 394).

Workup

  1. stirringstirred at 45° C. overnight
  2. extractionThe mixture was extracted with ethyl acetate (4×150 mL)
  3. dry with materialdried over Na2SO4
  4. filtrationfiltered
  5. concentrationconcentrated
  6. custompurified by column chromatography
  7. washeluting with a 1:2 mixture of ethyl acetate/hexanes
  8. concentrationThe concentrate of desired fractions
  9. stirringstirred for 2 h
  10. filtrationfiltered
  11. washwashed by hexane

Sources & evidence

ORD record
ord-019f5e49b3a74a8188609809d04d980c
Source dataset
uspto-grants-2011_03
Patent number
US07906529B2

Reaction notes

Loading…