Sodium hydride → HCID 10527851, compound

HRID 1489430Notes

Reaction equation

HRID 1489430 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]=[C:28]([F:30])[CH:27]=[CH:26][C:25]=1[C:31](=[O:42])[C@@H:32](OS(C(F)(F)F)(=O)=O)[CH3:33]>CN1CCCC1=O.O1CCCC1.C(O)(=O)C.C(OCC)(=O)C>[F:23][C:24]1[CH:29]=[C:28]([F:30])[CH:27]=[CH:26][C:25]=1[C:31](=[O:42])[C@H:32]([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])[CH3:33]

Participants

8

Reactant 3

HCID 24758Sodium hydrideHCID 10493689HCID 10493689, compoundHCID 10710636HCID 10710636, compound

Product 1

HCID 10527851HCID 10527851, compoundYield 38.5%

Reagents, catalysts & solvents 4

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

Procedure

1-[4-(2,2,3,3-Tetrafluoropropoxy)phenyl]-2(1H,3H)-imidazolone (6.58 g) was dissolved in 45 ml of 1-methyl-2-pyrrolidone, to which 0.86 g of 60% sodium hydride in oil was added. The mixture was stirred at room temperature for 15 hours. The ice-cooled mixture was added dropwise under nitrogen atmosphere over the period of 15 minutes to a solu- tion of 7.98 g of (2S)-2',4'-difluoro-2-trifluoromethanesulfonyloxypropiophenone in 150 ml of tetrahydrofuran which was cooled to -40° C. After the reaction temperature was raised to -20° C. over the period of 20 minutes, the reaction solution was stirred for 10 minutes. The reaction solution was diluted with 16 ml of acetic acid and 200 ml of ethyl acetate, washed with water (100 ml×2), 0.5N-hydrochloric acid (100 ml×2) and 100 ml of a saturated aqueous solution of sodium chloride successively, and dried over anhydrous magnesium chloride. After the solvent was distilled off under reduced pressure, the residue was purified by silica gel chromatography (silica gel: 1 kg, eluent; hexane:ethyl acetate:acetic acid=2:1:0.08) and recrystallized from 20 ml of diisopropyl ether to give 4 g of 1-[(1R)-2-(2,4-difluorophenyl)-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. temperaturewas cooled to -40° C
  3. temperatureAfter the reaction temperature was raised to -20° C. over the period of 20 minutes
  4. stirringthe reaction solution was stirred for 10 minutes
  5. washwashed with water (100 ml×2), 0.5N-hydrochloric acid (100 ml×2) and 100 ml of a saturated aqueous solution of sodium chloride successively
  6. dry with materialdried over anhydrous magnesium chloride
  7. distillationAfter the solvent was distilled off under reduced pressure
  8. customthe residue was purified by silica gel chromatography (silica gel: 1 kg, eluent; hexane:ethyl acetate:acetic acid=2:1:0.08)
  9. customrecrystallized from 20 ml of diisopropyl ether

Sources & evidence

ORD record
ord-6e63f10a85834e21bba392c6f9ae2750
Source dataset
uspto-grants-1997_10
Patent number
US05677464

Reaction notes

Loading…