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

HRID 599127Notes

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

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 (23.40 g, 36.73 mmol) in THF (180 mL) was added water (60 mL). The system was cooled to 0° C. To this cold solution was added LiOH.H2O (1.54 g, 36.73 mmol) and 30% H2O2 (16.65 mL, 146.92 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 (97.9 mL, 146.92 mmol) and stirred at room temperature for 15 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 (3×200 mL), dried over MgSO4, and concentrated in vacuo resulting in a crude mixture which was purified by ISCO silica gel column chromatography to yield (R)-2-[5-(3,5-difluoro-benzyloxy)-4′-trifluoromethyl-biphenyl-3-yl]-4-methyl-pentanoic acid (12.25 g, 70%).

Workup

temperaturemaintaining the internal temperature below 5° C
customThe excess H2O2 was quenched
stirringstirred at room temperature for 15 min
customThe organic solvent was removed in vacuo
additionby adding 1 N aqueous HCl solution
extractionThe aqueous layer was extracted with EtOAc (3×200 mL)
dry with materialdried over MgSO4
concentrationconcentrated in vacuo
customresulting in a crude mixture which
customwas purified by ISCO silica gel column chromatography

Sources & evidence

ORD record: ord-237e45b82b46430a8239ac007dbd66a5
Source dataset: uspto-grants-2011_03
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07897643B2

Reaction notes

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