Acetic Acid → HCID 10646750, compound

HRID 1489438Notes

Reaction equation

HRID 1489438 reaction equation
[F:1][C:2]([F:20])([CH:17]([F:19])[F:18])[CH2:3][O:4][C:5]1[CH:10]=[CH:9][C:8]([N:11]2[CH:15]=[CH:14][NH:13][C:12]2=[O:16])=[CH:7][CH:6]=1.[H-].[Na+].[F:23][C:24]1[CH:29]=[CH:28][CH:27]=[CH:26][C:25]=1[C:30](=[O:41])[C@@H:31](OS(C(F)(F)F)(=O)=O)[CH3:32].C(O)(=O)C>CN1CCCC1=O.O1CCCC1.C(OCC)(=O)C.C(OC(C)C)(C)C>[F:23][C:24]1[CH:29]=[CH:28][CH:27]=[CH:26][C:25]=1[C:30](=[O:41])[C@H:31]([N:13]1[CH:14]=[CH:15][N:11]([C:8]2[CH:9]=[CH:10][C:5]([O:4][CH2:3][C:2]([F:1])([F:20])[CH:17]([F:19])[F:18])=[CH:6][CH:7]=2)[C:12]1=[O:16])[CH3:32]

Participants

9

Reactant 4

HCID 176Acetic AcidHCID 24758Sodium hydrideHCID 10493689HCID 10493689, compoundHCID 10804132HCID 10804132, compound

Product 1

HCID 10646750HCID 10646750, compoundYield 37.2%

Reagents, catalysts & solvents 4

HCID 7914Diisopropyl EtherSolventHCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolventHCID 13387N-methyl-2-pyrrolidoneSolvent

Procedure

1-[4-(2,2,3,3-Tetrafluoropropoxy)phenyl]-2(1H,3H)-imidazolone (4.6 g) was dissolved in 30 ml of 1-methyl-2-pyrrolidone, to which 0.6 g of 60% sodium hydride in oil was added. The mixture was stirred at room temperature for 0.5 hours. The reaction solution was ice-cooled and added dropwise under nitrogen atmosphere over the period of 5 minutes to a solution of 5.3 g of (2S)-2'-fluoro-2-trifluoromethanesulfonyloxypropiophenone in 50 ml of tetrahydrofuran which was cooled to -40° C. Then, the reaction solution was stirred at -40° to -35° C. for 20 minutes. To the reaction solution was added 2 ml of acetic acid. The mixture was diluted with a mixture of 300 ml of ethyl acetate and 150 ml of diisopropyl ether, washed with 80 ml of water, 0.5N-hydrochloric acid (80 ml×2) and 40 ml of an aqueous solution of sodium chloride successively, and dried over anhydrous magnesium sulfate. The solvent was distilled off under reduced pressure. The residue was purified by silica gel chromatography (silica gel: 200 g, eluent; hexane:ethyl acetate:acetic acid=2:1:0.03) and crystallized from diisopropyl ether to give 2.6 g of 1-[(1R)-2-(2-fluorophenyl)-2-oxo-1-methylethyl]-3-[4-(2,2,3,3-tetrafluoropropoxy)phenyl]-2(1H,3H)-imidazolone as colorless powdery crystals.

Workup

  1. additionwas added
  2. temperaturecooled
  3. temperaturewas cooled to -40° C
  4. stirringThen, the reaction solution was stirred at -40° to -35° C. for 20 minutes
  5. washwashed with 80 ml of water, 0.5N-hydrochloric acid (80 ml×2) and 40 ml of an aqueous solution of sodium chloride successively
  6. dry with materialdried over anhydrous magnesium sulfate
  7. distillationThe solvent was distilled off under reduced pressure
  8. customThe residue was purified by silica gel chromatography (silica gel: 200 g, eluent; hexane:ethyl acetate:acetic acid=2:1:0.03)
  9. customcrystallized from diisopropyl ether

Sources & evidence

ORD record
ord-8692f1a5078b429e9011a2e39e4f95ba
Source dataset
uspto-grants-1997_10
Patent number
US05677464

Reaction notes

Loading…