Benzonitrile, 4-bromo- → 4-((1-(4-fluorophenyl)-1H-indazol-5-yl)(hydroxy)methyl)benzonitrile

HRID 563431Notes

Reaction equation

HRID 563431 reaction equation
Br[C:2]1[CH:9]=[CH:8][C:5]([C:6]#[N:7])=[CH:4][CH:3]=1.[Li]CCCC.[F:15][C:16]1[CH:21]=[CH:20][C:19]([N:22]2[C:30]3[C:25](=[CH:26][C:27]([CH:31]=[O:32])=[CH:28][CH:29]=3)[CH:24]=[N:23]2)=[CH:18][CH:17]=1>C1COCC1>[F:15][C:16]1[CH:17]=[CH:18][C:19]([N:22]2[C:30]3[C:25](=[CH:26][C:27]([CH:31]([OH:32])[C:2]4[CH:9]=[CH:8][C:5]([C:6]#[N:7])=[CH:4][CH:3]=4)=[CH:28][CH:29]=3)[CH:24]=[N:23]2)=[CH:20][CH:21]=1

Participants

5

Reactant 3

HCID 12162Benzonitrile, 4-bromo-HCID 579436121-(4-fluorophenyl)-1H-indazole-5-carbaldehydeHCID 178418339Butyllithium

Product 1

HCID 670055114-((1-(4-fluorophenyl)-1H-indazol-5-yl)(hydroxy)methyl)benzonitrileYield 52.4%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To solution of 4-bromobenzonitrile (182 mg, 1.0 mmol) in 5 mL of dry THF at −78° C. was added n-BuLi (0.7 mL of 1.6 M hexanes solution, 1.1 mmol). The reaction was stirred 30 min and then 1-(4-fluorophenyl)-1H-indazol-5-carboxaldehyde (240 mg, 1.0 mmol) was added and the reaction mixture was allowed to warm to RT. After 12 h, quenched with brine and extracted 2×EtOAc. The organic layers were dried over MgSO4, filtered, and concentrated. The residue was purified on SiO2 by MPLC eluting with a 0-30% EtOAc/hexane gradient to give 180 mg (52% yield) of 4-((1-(4-fluorophenyl)-1H-indazol-5-yl)(hydroxy)methyl)benzonitrile. MS found: (M+H)+=344.

Workup

  1. waitAfter 12 h
  2. customquenched with brine
  3. extractionextracted 2×EtOAc
  4. dry with materialThe organic layers were dried over MgSO4
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customThe residue was purified on SiO2 by MPLC
  8. washeluting with a 0-30% EtOAc/hexane gradient

Sources & evidence

ORD record
ord-6f8afc6a3f954ae0a09056ee7b16967a
Source dataset
uspto-grants-2011_11
Patent number
US08067447B2

Reaction notes

Loading…