Sodium hydride → HCID 10502524, compound

HRID 1489441Notes

Reaction equation

HRID 1489441 reaction equation
[F:1][C:2]([F:19])([O:6][C:7]1[CH:12]=[CH:11][C:10]([N:13]2[CH:17]=[CH:16][NH:15][C:14]2=[O:18])=[CH:9][CH:8]=1)[CH:3]([F:5])[F:4].[H-].[Na+].[F:22][C:23]1[CH:28]=[CH:27][CH:26]=[CH:25][C:24]=1[C:29](=[O:40])[C@@H:30](OS(C(F)(F)F)(=O)=O)[CH3:31]>CN1CCCC1=O.O1CCCC1.C(O)(=O)C.C(OCC)(=O)C.C(OC(C)C)(C)C>[F:22][C:23]1[CH:28]=[CH:27][CH:26]=[CH:25][C:24]=1[C:29](=[O:40])[C@H:30]([N:15]1[CH:16]=[CH:17][N:13]([C:10]2[CH:11]=[CH:12][C:7]([O:6][C:2]([F:1])([F:19])[CH:3]([F:4])[F:5])=[CH:8][CH:9]=2)[C:14]1=[O:18])[CH3:31]

Participants

9

Reactant 3

HCID 24758Sodium hydrideHCID 105643671-[4-(1,1,2,2-tetrafluoroethoxy)phenyl]-2(1H,3H)-imidazoloneHCID 10804132HCID 10804132, compound

Product 1

HCID 10502524HCID 10502524, compoundYield 34.1%

Reagents, catalysts & solvents 5

HCID 176Acetic AcidSolventHCID 7914Diisopropyl EtherSolventHCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolventHCID 13387N-methyl-2-pyrrolidoneSolvent

Procedure

1-[4-(1,1,2,2-Tetrafluoroethoxy)phenyl]-2(1H,3H)-imidazolone (9.7 g) was dissolved in 60 ml of 1-methyl-2-pyrrolidone, to which 1.08 g of 72% sodium hydride in oil was added. The mixture was stirred at room temperature for an hour. The reaction solution was ice-cooled and added dropwise under nitrogen atmosphere over the period of 25 minutes to a solution of 11.6 g of (2S)-2'-fluoro-2-trifluoromethanesulfonyloxypropiophenone in 100 ml of tetrahydrofuran which was cooled to -40° C. After the reaction temperature was raised to -35° C. over the period of 10 minutes, the reaction solution was stirred for 20 minutes. The reaction solution was diluted with 3 ml of acetic acid, 450 ml of ethyl acetate and 200 ml of diisopropyl ether, washed with water (250 ml×2), 0.5N-hydrochloric acid (150 ml×2) and 300 ml of a saturated aqueous solution of sodium chloride successively, and dried over anhydrous magnesium sulfate. After the solvent was distilled off under reduced pressure, the residue was purified by silica gel chromatography (eluent; hexane:ethyl acetate:acetic acid=2:1:0.04) and crystallized from diisopropyl ether to give 5.1 g of 1-[(1R)-2-(2-fluorophenyl)-2-oxo-1-methylethyl]-3-[4-(1,1,2,2-tetrafluoroethoxy)phenyl]-2(1H,3H)-imidazolone (yield: 34%) as colorless prisms.

Workup

  1. additionwas added
  2. temperaturecooled
  3. temperaturewas cooled to -40° C
  4. temperatureAfter the reaction temperature was raised to -35° C. over the period of 10 minutes
  5. stirringthe reaction solution was stirred for 20 minutes
  6. washwashed with water (250 ml×2), 0.5N-hydrochloric acid (150 ml×2) and 300 ml of a saturated aqueous solution of sodium chloride successively
  7. dry with materialdried over anhydrous magnesium sulfate
  8. distillationAfter the solvent was distilled off under reduced pressure
  9. customthe residue was purified by silica gel chromatography (eluent; hexane:ethyl acetate:acetic acid=2:1:0.04)
  10. customcrystallized from diisopropyl ether

Sources & evidence

ORD record
ord-2bb001c460674caf9e3956fdbd9ac93d
Source dataset
uspto-grants-1997_10
Patent number
US05677464

Reaction notes

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