Ammonium Chloride → 1-(4'-fluoro[1,1'-biphenyl]-3-yl)-1-(1-trityl-1H-imidazol-4-yl)-1-ethanol

HRID 1059164Notes

Reaction equation

HRID 1059164 reaction equation
Br[C:2]1[CH:3]=[C:4]([C:8]2[CH:13]=[CH:12][C:11]([F:14])=[CH:10][CH:9]=2)[CH:5]=[CH:6][CH:7]=1.C([Li])CCC.[C:20]([N:39]1[CH:43]=[C:42]([C:44](=[O:46])[CH3:45])[N:41]=[CH:40]1)([C:33]1[CH:38]=[CH:37][CH:36]=[CH:35][CH:34]=1)([C:27]1[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=1)[C:21]1[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=1.[Cl-].[NH4+]>C1COCC1.CCCCCC>[F:14][C:11]1[CH:12]=[CH:13][C:8]([C:4]2[CH:5]=[CH:6][CH:7]=[C:2]([C:44]([C:42]3[N:41]=[CH:40][N:39]([C:20]([C:27]4[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=4)([C:21]4[CH:22]=[CH:23][CH:24]=[CH:25][CH:26]=4)[C:33]4[CH:38]=[CH:37][CH:36]=[CH:35][CH:34]=4)[CH:43]=3)([OH:46])[CH3:45])[CH:3]=2)=[CH:9][CH:10]=1

Participants

7

Reactant 4

HCID 25517Ammonium ChlorideHCID 27569773-Bromo-4'-fluorobiphenylHCID 104280901-(1-trityl-1H-imidazol-4-yl)ethanoneHCID 178418339Butyllithium

Product 1

HCID 186685141-(4'-fluoro[1,1'-biphenyl]-3-yl)-1-(1-trityl-1H-imidazol-4-yl)-1-ethanolYield 55.2%

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolvent2×HCID 8058HexaneSolvent

Procedure

To a solution of 3-bromo-4′-fluoro-1,1′-biphenyl (1.50 g) in THF (20 ml) was added dropwise a solution (1.6 M; 3.73 ml) of n-butyllithium in hexane at −78° C., and the mixture was stirred for 20 min. A solution of 1-(1-trityl-1H-imidazol-4-yl)-1-ethanone (1.91 g) in THF (25 ml) was added dropwise at −78° C., and the mixture was stirred at −78° C. for 1 h, at −35 to −10° C. for 1 h and at 0° C. for 1 h. 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. The solvent was evaporated under reduced pressure and the residue was purified by column chomatography (eluent, hexane:ethyl acetate=3:1→1:1) and recrystallized from ethyl acetate-hexane to give the title compound (1.57 g) as colorless prism crystals.

Workup

  1. stirringthe mixture was stirred at −78° C. for 1 h, at −35 to −10° C. for 1 h and at 0° C. for 1 h
  2. extractionthe mixture was extracted with ethyl acetate
  3. washwashed with saturated brine
  4. customdried
  5. customThe solvent was evaporated under reduced pressure
  6. customthe residue was purified by column chomatography (eluent, hexane:ethyl acetate=3:1→1:1)
  7. customrecrystallized from ethyl acetate-hexane

Sources & evidence

ORD record
ord-6299ccd2a5dd4a02b8b88c7f37764663
Source dataset
uspto-grants-2003_02
Patent number
US06518257B1

Reaction notes

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