Acetic Acid → (3S,5S)-5-[(1R)-2-Benzyloxy-1-bromoethyl]-3-isopropyldihydrofuran-2-one

HRID 1694884Notes

Reaction equation

HRID 1694884 reaction equation
[Br:1]N1C(=O)CCC1=O.CN(C)C(=O)[C@H:12]([CH:25]([CH3:27])[CH3:26])[CH2:13]/[CH:14]=[CH:15]/[CH2:16][O:17][CH2:18][C:19]1[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=1.C(O)(=O)C.[C:34](=[O:37])(O)[O-:35].[Na+].S([O-])([O-])=O.[Na+].[Na+]>O.O1CCCC1>[CH2:18]([O:17][CH2:16][C@H:15]([C@H:14]1[O:35][C:34](=[O:37])[C@H:12]([CH:25]([CH3:27])[CH3:26])[CH2:13]1)[Br:1])[C:19]1[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=1

Participants

8

Reactant 5

HCID 176Acetic AcidHCID 24437Sodium SulfiteHCID 67184N-bromobutanimideHCID 516892Sodium BicarbonateHCID 66645901(2S,4E)-6-(Benzyloxy)-2-isopropylhex-4-enoic acid dimethylamide

Product 1

HCID 66645516(3S,5S)-5-[(1R)-2-Benzyloxy-1-bromoethyl]-3-isopropyldihydrofuran-2-oneYield 50%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent

Procedure

25.81 g of N-bromosuccinimide (145 mmol) was added to a solution of 21.20 g of (2S,4E)-6-(benzyloxy)-2-isopropylhex-4-enoic acid dimethylamide obtained in Example (1c) (72.5 mmol) and 8.3 ml of acetic acid (145 mmol) in a mixed solvent of tetrahydrofuran (290 ml) and water (145 ml) under ice-cooling, and the mixture was stirred at the same temperature for three hours. 100 ml of a saturated sodium bicarbonate aqueous solution and 100 ml of a 1.5 M sodium sulfite aqueous solution were added to the reaction mixture, and the mixture was further stirred at room temperature for 30 minutes. The reaction mixture was concentrated under reduced pressure to about ⅔ of the volume, followed by extraction with ethyl acetate. Then, the organic layer was washed with water and brine and dried over anhydrous magnesium sulfate. After filtration, the solvent was evaporated under reduced pressure, and the residue was purified by silica gel column chromatography (elution solvent:n-hexane/ethyl acetate=6/1-5/1) to obtain 22.73 g of the title compound (total yield over three steps: 50%).

Workup

  1. temperaturecooling
  2. stirringthe mixture was further stirred at room temperature for 30 minutes
  3. concentrationThe reaction mixture was concentrated under reduced pressure to about ⅔ of the volume
  4. extractionfollowed by extraction with ethyl acetate
  5. washThen, the organic layer was washed with water and brine
  6. dry with materialdried over anhydrous magnesium sulfate
  7. filtrationAfter filtration
  8. customthe solvent was evaporated under reduced pressure
  9. customthe residue was purified by silica gel column chromatography (elution solvent:n-hexane/ethyl acetate=6/1-5/1)

Sources & evidence

ORD record
ord-11603105355d43138f476c1084aa0f98
Source dataset
uspto-grants-2012_04
Patent number
US08158790B2

Reaction notes

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