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

HRID 599131Notes

Reaction equation

HRID 599131 reaction equation
C(C1COC(=O)N1[C:14](=[O:49])[CH:15]([C:20]1[CH:21]=[C:22]([C:39]2[CH:44]=[CH:43][C:42]([C:45]([F:48])([F:47])[F:46])=[CH:41][CH:40]=2)[CH:23]=[C:24]([O:26][CH2:27][C:28]2[CH:33]=[CH:32][C:31]([F:34])=[CH:30][C:29]=2[C:35]([F:38])([F:37])[F:36])[CH:25]=1)[CH2:16][CH:17]([CH3:19])[CH3:18])C1C=CC=CC=1.O[Li].O.OO.[O-:55]S([O-])=O.[Na+].[Na+]>C1COCC1.O>[F:34][C:31]1[CH:32]=[CH:33][C:28]([CH2:27][O:26][C:24]2[CH:25]=[C:20]([C@@H:15]([CH2:16][CH:17]([CH3:19])[CH3:18])[C:14]([OH:55])=[O:49])[CH:21]=[C:22]([C:39]3[CH:40]=[CH:41][C:42]([C:45]([F:47])([F:46])[F:48])=[CH:43][CH:44]=3)[CH:23]=2)=[C:29]([C:35]([F:37])([F:38])[F:36])[CH:30]=1

Participants

7

Reactant 4

HCID 784Hydrogen PeroxideHCID 24437Sodium SulfiteHCID 168937Lithium hydroxide, monohydrateHCID 765878014-Benzyl-3-{2-[5-(4-fluoro-2-trifluoromethyl-benzyloxy)-4'-trifluoromethyl-biphenyl-3-yl]-4-methyl-pentanoyl}-oxazolidin-2-one

Product 1

HCID 57667314(R)-2-[5-(4-Fluoro-2-trifluoromethyl-benzyloxy)-4'-trifluoromethyl-biphenyl-3-yl]-4-methyl-pentanoic acidYield 75.2%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
0 °C

Procedure

To a solution of 4-benzyl-3-{2-[5-(4-fluoro-2-trifluoromethyl-benzyloxy)-4′-trifluoromethyl-biphenyl-3-yl]-4-methyl-pentanoyl}-oxazolidin-2-one (0.535 g, 0.78 mmol) in THF (9 mL) was added water (3 mL). The system was cooled to 0° C. To this cold solution was added LiOH.H2O (33 mg, 0.78 mmol) and 30% H2O2 (0.354 mL, 3.12 mmol,) and stirred at 0° C. for 20 min. The excess H2O2 was quenched by adding 1.5 M aqueous Na2SO3 solution (2.08 mL, 3.12 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 (3×50 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 (R)-2-[5-(4-Fluoro-2-trifluoromethyl-benzyloxy)-4′-trifluoromethyl-biphenyl-3-yl]-4-methyl-pentanoic acid (310 mg).

Workup

  1. customThe excess H2O2 was quenched
  2. stirringstirred at room temperature for 5 min
  3. customThe organic solvent was removed in vacuo
  4. additionby adding 1 N aqueous HCl solution
  5. extractionThe aqueous layer was extracted with EtOAc (3×50 mL)
  6. dry with materialdried (MgSO4)
  7. concentrationThe mixture was concentrated in vacuo
  8. customwas purified by ISCO silica gel column chromatography

Sources & evidence

ORD record
ord-278d49063dfa4f948af29fb64ed8381d
Source dataset
uspto-grants-2011_03
Patent number
US07897643B2

Reaction notes

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