Hydrogen Peroxide → (S)-2-[5-(3,5-difluoro-benzyloxy)-4'-trifluoromethyl-biphenyl-3-yl]-4-methyl-pentanoic acid

HRID 599129Notes

Reaction equation

HRID 599129 reaction equation
C(C1COC(=O)N1[C:14](=[O:46])[CH:15]([C:20]1[CH:21]=[C:22]([C:36]2[CH:41]=[CH:40][C:39]([C:42]([F:45])([F:44])[F:43])=[CH:38][CH:37]=2)[CH:23]=[C:24]([O:26][CH2:27][C:28]2[CH:33]=[C:32]([F:34])[CH:31]=[C:30]([F:35])[CH:29]=2)[CH:25]=1)[CH2:16][CH:17]([CH3:19])[CH3:18])C1C=CC=CC=1.O[Li].O.OO.[O-:52]S([O-])=O.[Na+].[Na+]>C1COCC1.O>[F:34][C:32]1[CH:33]=[C:28]([CH:29]=[C:30]([F:35])[CH:31]=1)[CH2:27][O:26][C:24]1[CH:25]=[C:20]([C@H:15]([CH2:16][CH:17]([CH3:19])[CH3:18])[C:14]([OH:46])=[O:52])[CH:21]=[C:22]([C:36]2[CH:41]=[CH:40][C:39]([C:42]([F:44])([F:43])[F:45])=[CH:38][CH:37]=2)[CH:23]=1

Participants

7

Reactant 4

HCID 784Hydrogen PeroxideHCID 24437Sodium SulfiteHCID 168937Lithium hydroxide, monohydrateHCID 672665294-Benzyl-3-{2-[5-(3,5-difluoro-benzyloxy)-4'-trifluoromethyl-biphenyl-3-yl]-4-methyl-pentanoyl}-oxazolidin-2-one

Product 1

HCID 25264360(S)-2-[5-(3,5-difluoro-benzyloxy)-4'-trifluoromethyl-biphenyl-3-yl]-4-methyl-pentanoic acidYield 92%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
0 °C

Procedure

To a solution of 4-benzyl-3-{2-[5-(3,5-difluoro-benzyloxy)-4′-trifluoromethyl-biphenyl-3-yl]-4-methyl-pentanoyl}-oxazolidin-2-one (0.425 g, 0.67 mmol) in THF (10 mL) was added water (3.5 mL). The system was cooled to 0° C. To this cold solution was added LiOH.H2O (0.028 g, 0.67 mmol) and 30% H2O2 (304 mL, 2.68 mmol), drop-wise, maintaining the internal temperature below 5° C. The resulting cloudy solution was stirred at 0° C. for 20 min. The excess H2O2 was quenched by adding 1.5 M aqueous Na2SO3 solution (1.79 mL, 2.68 mmol) and stirred at room temperature for 5 min. The organic solvent was removed in vacuo. The resulting liquid was acidified to pH 2 by adding 1 N aqueous HCl solution. The aqueous layer was extracted with EtOAc (3×25 mL) and dried (MgSO4). The mixture was concentrated in vacuo to receive a crude mixture which was purified by ISCO silica gel column chromatography to yield (S)-2-[5-(3,5-difluoro-benzyloxy)-4′-trifluoromethyl-biphenyl-3-yl]-4-methyl-pentanoic acid (0.295 g, 92%).

Workup

  1. temperaturemaintaining the internal temperature below 5° C
  2. customThe excess H2O2 was quenched
  3. stirringstirred at room temperature for 5 min
  4. customThe organic solvent was removed in vacuo
  5. additionby adding 1 N aqueous HCl solution
  6. extractionThe aqueous layer was extracted with EtOAc (3×25 mL)
  7. dry with materialdried (MgSO4)
  8. concentrationThe mixture was concentrated in vacuo
  9. customwas purified by ISCO silica gel column chromatography

Sources & evidence

ORD record
ord-0e27b193f3ac4878b19823c488459239
Source dataset
uspto-grants-2011_03
Patent number
US07897643B2

Reaction notes

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