Hexamethylphosphoramide → (3S,5R)-3-Allyl-5-(4-fluoro-3-methylphenyl)dihydrofuran-2(3H)-one

HRID 1643280Notes

Reaction equation

HRID 1643280 reaction equation
C[Si]([N-][Si](C)(C)C)(C)C.[Li+].[F:11][C:12]1[CH:17]=[CH:16][C:15]([C@@H:18]2[O:22][C:21](=[O:23])[CH2:20][CH2:19]2)=[CH:14][C:13]=1[CH3:24].Br[CH2:26][CH:27]=[CH:28]C.CN(P(N(C)C)(N(C)C)=O)C>C1COCC1>[CH2:28]([C@H:20]1[CH2:19][C@H:18]([C:15]2[CH:16]=[CH:17][C:12]([F:11])=[C:13]([CH3:24])[CH:14]=2)[O:22][C:21]1=[O:23])[CH:27]=[CH2:26]

Participants

6

Reactant 4

HCID 12679HexamethylphosphoramideHCID 1224142-Butene, 1-bromo-HCID 2733832Lithium HexamethyldisilazideHCID 59568816(R)-5-(4-fluoro-3-methyl-phenyl)-dihydro-furan-2-one

Product 1

HCID 59568768(3S,5R)-3-Allyl-5-(4-fluoro-3-methylphenyl)dihydrofuran-2(3H)-one

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent3×

Conditions

Temperature
-70 °C

Procedure

To a solution of lithium bis(trimethylsilyl)amide (1.2 mmol) in anhydrous THF (20 mL) was added (R)-5-(4-fluoro-3-methyl-phenyl)-dihydro-furan-2-one (194 mg) in 1 mL THF at −70° C. over a period of 15 minutes. After completing the addition, the mixture was stirred for an additional 20 min at −70° C. and then for 10 min at room temperature. The mixture was cooled down again to −70° C. and a pre-cooled solution of 200 mg 1-bromo-but-2-ene and 400 μL HMPA in 1 mL THF slowly added. The mixture was further stirred at −70° C. for 2 h and the temperature was slowly raised to room temperature over a period of 2 h. The reaction was quenched by pouring into saturated NH4Cl (20 mL) and followed extraction with ethyl acetate (3×30 mL). The combined organic layers were washed with 20 mL brine twice and dried over Na2SO4. The solvent was removed under reduced pressure and the product isolated by flash column chromatographed eluting with 0% to 50% ethyl acetate/hexane gradient solvent to give the anti/syn products (94:6 ratios).

Workup

  1. additionthe addition
  2. waitfor 10 min at room temperature
  3. temperatureThe mixture was cooled down again to −70° C.
  4. stirringThe mixture was further stirred at −70° C. for 2 h
  5. temperaturethe temperature was slowly raised to room temperature over a period of 2 h
  6. customThe reaction was quenched
  7. additionby pouring into saturated NH4Cl (20 mL)
  8. extractionextraction with ethyl acetate (3×30 mL)
  9. washThe combined organic layers were washed with 20 mL brine twice
  10. dry with materialdried over Na2SO4
  11. customThe solvent was removed under reduced pressure
  12. customthe product isolated by flash column
  13. customchromatographed
  14. washeluting with 0% to 50% ethyl acetate/hexane gradient solvent
  15. customto give the anti/syn products (94:6 ratios)

Sources & evidence

ORD record
ord-0fbaa64decbb4b989bf31e4058bb0170
Source dataset
uspto-grants-2012_02
Patent number
US08119692B2

Reaction notes

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