Benzyl Bromide → HCID 68313099, compound

HRID 1530437Notes

Reaction equation

HRID 1530437 reaction equation
[CH3:1][CH:2]1[CH2:6][CH2:5][O:4][C:3]1=[O:7].[OH-:8].[K+].[H-].[Na+].Br[CH2:13][C:14]1[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=1>O1CCOCC1.CN(C=O)C>[CH2:13]([O:8][C:3](=[O:7])[CH:2]([CH3:1])[CH2:6][CH2:5][O:4][CH2:13][C:14]1[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=1)[C:14]1[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=1

Participants

7

Reactant 4

HCID 7498Benzyl BromideHCID 14797Potassium HydroxideHCID 24758Sodium hydrideHCID 98323alpha-Methylbutyrolactone

Product 1

HCID 68313099HCID 68313099, compoundYield 25%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 312751,4-DioxaneSolvent

Procedure

To a solution of 3-methyldihydrofuran-2-one (2.0 g, 20.0 mmol) in dioxane (15 mL) was added a solution of KOH (1.32 g, 20.0 mmol in 5 mL of water) and the mixture was stirred at RT for 30 min, then at 90° C. for 15 min. After cooling to RT, volatiles were removed under reduced pressure and the residue was azeotroped with toluene and heated at 190° C. affording a white residue. The resulting residue was suspended in DMF (25 mL) and NaH (800 mg, 20 mmol) was added at RT over 5 min. The mixture was stirred at RT for 30 min, then bromomethylbenzene (5.94 mL, 50 mmol) was added over 5 min. Stirring at RT was continued for 18 h then the mixture was partitioned between EtOAc and water. The aqueous phase was extracted with EtOAc (×2) and the combined organic layers were washed with water, followed by brine, then dried (Na2SO4) and concentrated in vacuo. Half of the resulting residue was purified by column chromatography (Si-PCC, gradient 2-30% EtOAc in cyclohexane) affording 4-Benzyloxy-2-methylbutyric acid benzyl ester as a colorless oil (0.738 g, 25%). 1H NMR (CDCl3, 400 MHz): δ 7.38-7.22 (10H, m), 5.08 (2H, s), 4.44 (2H, s), 3.51-3.44 (2H, m), 2.78-2.64 (1H, m), 2.12-1.97 (1H, m), 1.79-1.64 (1H, m), 1.19 (3H, d, J=7.06 Hz).

Workup

  1. waitat 90° C. for 15 min
  2. temperatureAfter cooling to RT
  3. customvolatiles were removed under reduced pressure
  4. customthe residue was azeotroped with toluene
  5. temperatureheated at 190° C.
  6. customaffording a white residue
  7. stirringThe mixture was stirred at RT for 30 min
  8. stirringStirring at RT
  9. waitwas continued for 18 h
  10. customthe mixture was partitioned between EtOAc and water
  11. extractionThe aqueous phase was extracted with EtOAc (×2)
  12. washthe combined organic layers were washed with water
  13. dry with materialdried (Na2SO4)
  14. concentrationconcentrated in vacuo
  15. customHalf of the resulting residue was purified by column chromatography (Si-PCC, gradient 2-30% EtOAc in cyclohexane)

Sources & evidence

ORD record
ord-3234883f3bbf41b48da3ff2c0d9cd352
Source dataset
uspto-grants-2015_07
Patent number
US09090628B2

Reaction notes

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