Sodium hydride → 4-(3-Fluorophenyl)-2,2-dimethyl-5-(4-(methylthio)phenyl)furan-3(2H)-one

HRID 2298315Notes

Reaction equation

HRID 2298315 reaction equation
[F:1][C:2]1[CH:3]=[C:4]([CH2:8][C:9]([C:11]2[CH:16]=[CH:15][C:14]([S:17][CH3:18])=[CH:13][CH:12]=2)=[O:10])[CH:5]=[CH:6][CH:7]=1.[H-].[Na+].Br[C:22]([CH3:28])([CH3:27])[C:23](C#N)=[O:24]>C1COCC1>[CH3:27][C:22]1([CH3:28])[C:23](=[O:24])[C:8]([C:4]2[CH:5]=[CH:6][CH:7]=[C:2]([F:1])[CH:3]=2)=[C:9]([C:11]2[CH:16]=[CH:15][C:14]([S:17][CH3:18])=[CH:13][CH:12]=2)[O:10]1

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 118178202-(3-Fluorophenyl)-1-(4-(methylthio)phenyl)ethanoneHCID 124878382-Bromo-2-methylpropanoyl cyanide

Product 1

HCID 183855844-(3-Fluorophenyl)-2,2-dimethyl-5-(4-(methylthio)phenyl)furan-3(2H)-oneYield 80.9%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

To a stirred solution of 2-(3-fluorophenyl)-1-{4-(methylthio)phenyl}-ethan-1-one (100 g) in 1 L dry THF, was added portion-wise 26 g of 95 % sodium hydride at 0° C. The reaction solution was stirred at the same temperature for 1 hour. Then 69 g of α-bromo-isobutyryl cyanide diluted in 25 ml dry THF was added dropwise to the stirred solution at 0° C. The reaction mixture was stirred overnight while allowing to warm gradually to room temperature. The solution was concentrated in vacuo, to which was added 50 ml water. The aqueous solution was extracted with ethylacetate (1 L). The organic layer was concentrated in vacuo and purified by column chromatography (hexane/ethylacetate=6:1) to give 102 g of 2,2-dimethyl-4-(3-fluorophenyl)-5-{4-(methylthio)phenyl}-3(2H)-furanone. mp: 106° C. NMR: δ1.55 (s, 6H), 2.50 (s. 3H), 6.97-7.11 (m, 3H), 7.18 (d, J=9.0 Hz, 2H), 7.26-7.36 (m, 1H), 7.55 (d, J=9.0 Hz, 2H).

Workup

  1. additionwas added dropwise to the stirred solution at 0° C
  2. stirringThe reaction mixture was stirred overnight
  3. concentrationThe solution was concentrated in vacuo, to which
  4. additionwas added 50 ml water
  5. extractionThe aqueous solution was extracted with ethylacetate (1 L)
  6. concentrationThe organic layer was concentrated in vacuo
  7. custompurified by column chromatography (hexane/ethylacetate=6:1)

Sources & evidence

ORD record
ord-b434d05ade254b1c99dbafdb415a9deb
Source dataset
uspto-grants-2002_12
Patent number
US06492416B1

Reaction notes

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