3-Bromo-2-methyl-1-propene → 4-Benzyl-3-[2-(5-benzyloxy-4'-trifluoromethyl-biphenyl-3-yl)-4-methyl-pent-4-enoyl]-oxazolidin-2-one

HRID 889707Notes

Reaction equation

HRID 889707 reaction equation
[CH2:1]([CH:8]1[CH2:12][O:11][C:10](=[O:13])[N:9]1[C:14](=[O:40])[CH2:15][C:16]1[CH:17]=[C:18]([C:30]2[CH:35]=[CH:34][C:33]([C:36]([F:39])([F:38])[F:37])=[CH:32][CH:31]=2)[CH:19]=[C:20]([O:22][CH2:23][C:24]2[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=2)[CH:21]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.Br[CH2:42][C:43]([CH3:45])=[CH2:44]>C1COCC1>[CH2:1]([CH:8]1[CH2:12][O:11][C:10](=[O:13])[N:9]1[C:14](=[O:40])[CH:15]([C:16]1[CH:17]=[C:18]([C:30]2[CH:31]=[CH:32][C:33]([C:36]([F:38])([F:39])[F:37])=[CH:34][CH:35]=2)[CH:19]=[C:20]([O:22][CH2:23][C:24]2[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=2)[CH:21]=1)[CH2:44][C:43]([CH3:45])=[CH2:42])[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1

Participants

4

Reactant 2

HCID 3577853-Bromo-2-methyl-1-propeneHCID 666982364-Benzyl-3-[2-(5-benzyloxy-4'-trifluoromethyl-biphenyl-3-yl)-acetyl]-oxazolidin-2-one

Product 1

HCID 666982644-Benzyl-3-[2-(5-benzyloxy-4'-trifluoromethyl-biphenyl-3-yl)-4-methyl-pent-4-enoyl]-oxazolidin-2-oneYield 95%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
-78 °C

Procedure

To a colorless solution of 4-benzyl-3-[2-(5-benzyloxy-4′-trifluoromethyl-biphenyl-3-yl)-acetyl]-oxazolidin-2-one from the previous step (6.0 g, 11.00 mmol) in dry THF (22 mL) at −78° C. was added sodium bis(trimethylsiyl)amide (NaHMDS) (1 M in THF solution, 12.11 mL, 12.11 mmol), drop-wise, maintaining the internal temperature below −75° C. The resulting red solution was stirred at −78° C. for 30 minutes. To this was added 3-bromo-2-methyl propene (4.44 mL, 44 mmol) maintaining the temperature below −75° C. When the addition was near completion, the reaction mixture turned green. At this point the dry-ice bath was quickly removed and replaced with water-ice bath, and the addition was completed. The reaction mixture was stirred at 0° C. for an additional 30 min and quenched with saturated aqueous NH4Cl solution. The system was diluted with EtOAC (100 mL) and the organic phase was washed with saturated aqueous NaHCO3 solution (3×50 mL) and dried (MgSO4). Solvent was removed in vacuo and the crude mixture was purified by ISCO silica gel column to yield 4-benzyl-3-[2-(5-benzyloxy-4′-trifluoromethyl-biphenyl-3-yl)-4-methyl-pent-4-enoyl]-oxazolidin-2-one (6.3 g, 95%).

Workup

  1. temperaturemaintaining the internal temperature below −75° C
  2. temperaturemaintaining the temperature below −75° C
  3. additionWhen the addition
  4. customAt this point the dry-ice bath was quickly removed
  5. customreplaced with water-ice bath
  6. additionthe addition
  7. stirringThe reaction mixture was stirred at 0° C. for an additional 30 min
  8. customquenched with saturated aqueous NH4Cl solution
  9. additionThe system was diluted with EtOAC (100 mL)
  10. washthe organic phase was washed with saturated aqueous NaHCO3 solution (3×50 mL)
  11. dry with materialdried (MgSO4)
  12. customSolvent was removed in vacuo
  13. customthe crude mixture was purified by ISCO silica gel column

Sources & evidence

ORD record
ord-98b0bbacac83439a9007afb941d1ab20
Source dataset
uspto-grants-2012_08
Patent number
US08252935B2

Reaction notes

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