Tetrahydrofuran → HCID 178489084, compound

HRID 2418500Notes

Reaction equation

HRID 2418500 reaction equation
C(OC(N1C(C2C=CC(OC)=CC=2)=C([C:19]2[CH:24]=[CH:23][CH:22]=[CH:21][C:20]=2[F:25])N=C1)C)C.C[N:27]([CH3:33])[CH2:28][CH2:29][N:30](C)C.[CH2:34]([Li])[CH2:35][CH2:36][CH3:37].C[Si](C)(C)[N:41]=[C:42]([C:47]([F:50])([F:49])[F:48])[C:43]([F:46])([F:45])[F:44].[C:53](=[O:56])(O)[O-].[Na+].O1CC[CH2:60][CH2:59]1>>[F:25][C:20]1[CH:21]=[CH:22][C:23]([C:29]2[N:30]=[C:33]([C:42]([C:47]([F:50])([F:49])[F:48])([C:43]([F:46])([F:45])[F:44])[NH2:41])[NH:27][C:28]=2[C:34]2[CH:60]=[CH:59][C:37]([O:56][CH3:53])=[CH:36][CH:35]=2)=[CH:24][CH:19]=1

Participants

7

Reactant 6

HCID 8028TetrahydrofuranHCID 8037N,N,N',N'-TetramethylethylenediamineHCID 516892Sodium BicarbonateHCID 13274636[1,1-Di(trifluoromethyl)methyleneamino]trimethylsilaneHCID 204461171-(1-ethoxy-ethyl)-4-(fluorophenyl)-5-(4-methoxyphenyl)-1H-imidazoleHCID 178418339Butyllithium

Product 1

HCID 178489084HCID 178489084, compoundYield 51.5%

Conditions

Temperature
-78 °C

Procedure

To a cooled (-78° C.) solution of 1-(1-ethoxy-ethyl)-4-(fluorophenyl)-5-(4-methoxyphenyl)-1H-imidazole (5.0 g, 14.8 mmoles) and tetramethylethylenediamine (2.60 ml, 17.0 mmoles) in 75 ml of tetrahydrofuran was added 12.1 ml of 2.1M n-butyl lithium dropwise. The mixture was stirred for 15 minutes at -78° C., and then N-(trimethylsilyl)hexafluoroacetone imine (5.84 g, 24.6 mmoles) was added dropwise. After stirring for an additional hour at -78° C., the mixture was warmed to 0° C. Then, 55 ml of saturated sodium bicarbonate was added dropwise and the reaction mixture was brought to room temperature. The organic layer was separated and the solvent removed in vacuo. The residue was stirred overnight with a mixture of 110 ml of ethanol and 55 ml of 2N hydrochloric acid. The ethanol was removed under vacuum. The aqueous residue was extracted thoroughly with ether, dried over anhydrous magnesium sulfate and concentrated to dryness to afford 5.42 g (84%) of crude product. The residual oil was chromatographed on silica gel eluting with ether/hexane (1:4). The product fractions were recrystallized from butyl chloride/hexane to give 3.3 g (51.5%) of the title compound as white crystals, m.p. 123°-124° C.

Workup

  1. stirringAfter stirring for an additional hour at -78° C.
  2. temperaturethe mixture was warmed to 0° C
  3. customwas brought to room temperature
  4. customThe organic layer was separated
  5. customthe solvent removed in vacuo
  6. stirringThe residue was stirred overnight with a mixture of 110 ml of ethanol and 55 ml of 2N hydrochloric acid
  7. customThe ethanol was removed under vacuum
  8. extractionThe aqueous residue was extracted thoroughly with ether
  9. dry with materialdried over anhydrous magnesium sulfate
  10. concentrationconcentrated to dryness
  11. customto afford 5.42 g (84%) of crude product
  12. customThe residual oil was chromatographed on silica gel eluting with ether/hexane (1:4)
  13. customThe product fractions were recrystallized from butyl chloride/hexane

Sources & evidence

ORD record
ord-9d0a5f7f5d1a45a9a88713c59cd85cc8
Source dataset
uspto-grants-1984_09
Patent number
US04472422

Reaction notes

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