Sodium hydride → 2H-Pyran, 2-[(1R)-1-[2-(2,4-difluorophenyl)oxiranyl]ethoxy]tetrahydro-

HRID 1654198Notes

Reaction equation

HRID 1654198 reaction equation
[H-].[Na+].[I-].[CH3:4][S+](C)(C)=O.[F:9][C:10]1[CH:15]=[C:14]([F:16])[CH:13]=[CH:12][C:11]=1[C:17](=[O:27])[C@H:18]([O:20][CH:21]1[CH2:26][CH2:25][CH2:24][CH2:23][O:22]1)[CH3:19]>CS(C)=O>[O:22]1[CH2:23][CH2:24][CH2:25][CH2:26][CH:21]1[O:20][C@@H:18]([C:17]1([C:11]2[CH:12]=[CH:13][C:14]([F:16])=[CH:15][C:10]=2[F:9])[CH2:4][O:27]1)[CH3:19]

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 74498Sulfoxonium, trimethyl-, iodide (1:1)HCID 10199305(2R)-1-(2,4-difluorophenyl)-2-((tetrahydro-2H-pyran-2-yl)oxy)propan-1-one

Product 1

HCID 542112042H-Pyran, 2-[(1R)-1-[2-(2,4-difluorophenyl)oxiranyl]ethoxy]tetrahydro-Yield 91.2%

Reagents, catalysts & solvents 1

HCID 679Dimethyl SulfoxideSolvent2×

Conditions

Temperature
15 °C

Procedure

To dimethyl sulfoxide (50 ml) was added 60% sodium hydride (0.833 g) in mineral oil. While stirring the mixture at about 15° C., trimethylsulfoxonium iodide (4.80 g) was added thereto, which was stirred for 15 minutes at room temperature. The reaction mixture was cooled with ice, to which was added a dimethyl sulfoxide solution (10 ml) of (2R)-2',4'-difluoro-2-(3,4,5,6-tetrahydro-2H-pyran-2-yloxy)propiophenone (4.90 g). The resultant mixture was stirred for two hours at room temperature. The reaction mixture was poured into ice-water (120 ml), followed by extraction with ethyl acetate (150 ml, 100 ml, 100ml). Ethyl acetate layers were combined and washed with water (50 ml) and a saturated aqueous solution of sodium chloride (50 ml), followed by drying over anhydrous magnesium sulfate. The solvent was distilled off under reduced pressure, and the residue was purified by means of a silica gel chromatography (eluent: hexane-ethyl acetate=10:1) to afford 2-[(1R)-1-(3,4,5,6 -tetrahydro-2H-pyran-2-yloxy)ethyl]-2-(2,4-difluorophenyl)oxirane (4.70 g) as a pale yellow oily product.

Workup

  1. stirringwhich was stirred for 15 minutes at room temperature
  2. temperatureThe reaction mixture was cooled with ice, to which
  3. extractionfollowed by extraction with ethyl acetate (150 ml, 100 ml, 100ml)
  4. washwashed with water (50 ml)
  5. dry with materialby drying over anhydrous magnesium sulfate
  6. distillationThe solvent was distilled off under reduced pressure
  7. customthe residue was purified by means of a silica gel chromatography (eluent: hexane-ethyl acetate=10:1)

Sources & evidence

ORD record
ord-7b551310e1814652b2b25148c8998a1e
Source dataset
uspto-grants-1995_04
Patent number
US05405861

Reaction notes

Loading…