Hexafluoroacetone → HCID 13580030, compound

HRID 482914Notes

Reaction equation

HRID 482914 reaction equation
[C:1]1([C:7]2[N:8]=[CH:9][N:10](C(OCC)C)[C:11]=2[C:12]2[CH:17]=[CH:16][C:15]([S:18][CH3:19])=[CH:14][CH:13]=2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.C([Li])CCC.[F:30][C:31]([F:39])([F:38])[C:32]([C:34]([F:37])([F:36])[F:35])=[O:33].C(=O)(O)[O-].[Na+]>O1CCCC1.CCCCCC>[C:1]1([C:7]2[N:8]=[C:9]([C:32]([C:34]([F:37])([F:36])[F:35])([C:31]([F:39])([F:38])[F:30])[OH:33])[NH:10][C:11]=2[C:12]2[CH:17]=[CH:16][C:15]([S:18][CH3:19])=[CH:14][CH:13]=2)[CH:2]=[CH:3][CH:4]=[CH:5][CH:6]=1

Participants

7

Reactant 4

HCID 12695HexafluoroacetoneHCID 516892Sodium BicarbonateHCID 543654074-Phenyl-5-(4-methylthiophenyl)-1-(alpha-ethoxyethyl)imidazoleHCID 178418339Butyllithium

Product 1

HCID 13580030HCID 13580030, compound

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolventHCID 8058HexaneSolvent

Procedure

To a stirred solution of 4-phenyl-5-(4-methylthiophenyl)-1-(α-ethoxyethyl)imidazole (15.5 g, 0.05 mole) in 175 ml of dry tetrahydrofuran was added 7.95 ml (0.052 mole) of N,N-tetramethylethylenediamine. The reaction mixture was cooled to -78° and 45.9 ml of 1.6 M n-butyl lithium in hexane was added dropwise. After stirring the mixture an additional 15 minutes, hexafluoroacetone (12.2 ml) was condensed in a jacketed addition funnel and added dropwise. The mixture was stirred for 1 hour with continued cooling and then 200 ml of saturated aqueous sodium bicarbonate solution was added dropwise. The reaction was warmed to room temperature, and the organic layer was separated. The solvent was evaporated in vacuo and the residue was stirred in 300 ml of ethanol and 300 ml of 2N aqueous hydrochloric acid. The ethanol was removed in vacuo and the reaction mixture was basified to pH=8 with saturated aqueous potassium carbonate. The product was extracted into ether, washed with 10% aqueous sodium bicarbonate and dried over anhydrous potassium carbonate. After concentration in vacuo, the residue was purified by flash chromatography on silica gel (85:15 hexane/ethyl acetate) followed by trituration with petroleum ether to afford 12.3 g of 4-phenyl-5-(4-methylthiophenyl)-α,α-bis(trifluoromethyl)-1H-imidazole-2-methanol, m.p. 119°-121°.

Workup

  1. temperatureThe reaction mixture was cooled to -78°
  2. customcondensed in a jacketed addition funnel
  3. additionadded dropwise
  4. temperaturewith continued cooling
  5. customthe organic layer was separated
  6. customThe solvent was evaporated in vacuo
  7. stirringthe residue was stirred in 300 ml of ethanol
  8. customThe ethanol was removed in vacuo
  9. extractionThe product was extracted into ether
  10. washwashed with 10% aqueous sodium bicarbonate
  11. dry with materialdried over anhydrous potassium carbonate
  12. concentrationAfter concentration in vacuo
  13. customthe residue was purified by flash chromatography on silica gel (85:15 hexane/ethyl acetate)

Sources & evidence

ORD record
ord-e820fac513fa4d92b682fe8e0939178a
Source dataset
uspto-grants-1986_03
Patent number
US04576958

Reaction notes

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