Ammonium Chloride → 7-(4'-Fluoro[1,1'-biphenyl]-3-yl)-6,7-dihydro-5h-pyrrolo[1,2-c]imidazol-7-ol

HRID 724221Notes

Reaction equation

HRID 724221 reaction equation
C([Li])CCC.Br[C:7]1[CH:8]=[C:9]([C:13]2[CH:18]=[CH:17][C:16]([F:19])=[CH:15][CH:14]=2)[CH:10]=[CH:11][CH:12]=1.[CH:20]1[N:24]=[CH:23][N:22]2[CH2:25][CH2:26][C:27](=[O:28])[C:21]=12.[Cl-].[NH4+]>CCCCCC.C1COCC1>[F:19][C:16]1[CH:17]=[CH:18][C:13]([C:9]2[CH:10]=[CH:11][CH:12]=[C:7]([C:27]3([OH:28])[C:21]4[N:22]([CH:23]=[N:24][CH:20]=4)[CH2:25][CH2:26]3)[CH:8]=2)=[CH:14][CH:15]=1

Participants

7

Reactant 4

HCID 25517Ammonium ChlorideHCID 27569773-Bromo-4'-fluorobiphenylHCID 111709605,6-Dihydropyrrolo[1,2-c]imidazol-7-oneHCID 178418339Butyllithium

Product 1

HCID 97961407-(4'-Fluoro[1,1'-biphenyl]-3-yl)-6,7-dihydro-5h-pyrrolo[1,2-c]imidazol-7-olYield 45.1%

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolvent2×HCID 8058HexaneSolvent

Conditions

Temperature
-78 °C

Procedure

A solution (1.6 M; 1.98 ml) of n-butyl lithium in hexane was gently added dropwise to a solution of 3-bromo-4′-fluoro-1,1′-biphenyl (753 mg) in THF (10 ml) at −78° C., and the mixture was stirred at −78° C. for 30 min. A solution of 5,6-dihydro-7Hpyrrolo[1,2-c]imidazol-7-one (244 mg) in THF (10 ml) solution was gently added dropwise and the mixture was stirred at −78° C. for 1 h. A saturated aqueous ammonium chloride solution was added to the reaction mixture and the mixture was extracted with ethyl acetate, washed with saturated brine, and dried over anhydrous magnesium sulfate. The solvent was evaporated under reduced pressure and the residue was purified by silica gel column chromatography (eluent, ethyl acetate→ethyl acetate:methanol=5:1) and recrystallized from acetone-hexane to give the title compound (265 mg) as colorless needle crystals.

Workup

  1. stirringthe mixture was stirred at −78° C. for 1 h
  2. extractionthe mixture was extracted with ethyl acetate
  3. washwashed with saturated brine
  4. dry with materialdried over anhydrous magnesium sulfate
  5. customThe solvent was evaporated under reduced pressure
  6. customthe residue was purified by silica gel column chromatography (eluent, ethyl acetate→ethyl acetate:methanol=5:1)
  7. customrecrystallized from acetone-hexane

Sources & evidence

ORD record
ord-6d5d550a3d10474193688d5d4178dcce
Source dataset
uspto-grants-2006_11
Patent number
US07141598B2

Reaction notes

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