Hydrogen Peroxide → (R)-2-(4-fluorophenyl)propanoic acid

Temperature

0 °C

To a solution of (4R)-3-[(2R)-2-(4-fluorophenyl )propanoyl]-4-isopropyl-1,3-oxazolidin-2-one (2.59 g, 9.28 mmol) in 160 mL THF/H2O (3:1) at 0° C., was added 30% H2O2 (8.4 mL, 74.2 mmol) followed by LiOH (780 mg, 18.6 mmol). The resulting mixture was stirred at 0° C. for 2 h and the excess peroxide was quenched at 0° C. with 1.5 N aqueous Na2SO3 (54 mL). After buffering to pH 9–10 with aqueous NaHCO3 and evaporation of the THF, the oxazolidone chiral auxiliary was recovered by EtOAc extraction (50 mL×3). The aqueous layer was acidified with 3N HCl and extracted with EtOAc. The organic layer was washed with brine, dried over MgSO4, filtered and concentrated in vacuo to give 1.43 g (8.51 mmol, 92%) of (2R)-2-(4-fluorophenyl)propanoic acid; [α]D=−61.5° (C=1.04, MeOH): 1H NMR (400 MHz, CDCl3) δ 12.2–11.4 (br, 1H), 7.31–7.24 (m, 2H), 7.04–6.97 (m, 2H), 3.72 (q, 1H, J=7.3 Hz), 1.49 (d, 3H, J=7.3 Hz); ESMS m/e: 167.2 (M−H)+.

1. customthe excess peroxide was quenched at 0° C. with 1.5 N aqueous Na2SO3 (54 mL)
2. customAfter buffering to pH 9–10 with aqueous NaHCO3 and evaporation of the THF
3. customthe oxazolidone chiral auxiliary was recovered by EtOAc extraction (50 mL×3)
4. extractionextracted with EtOAc
5. washThe organic layer was washed with brine
6. dry with materialdried over MgSO4
7. filtrationfiltered
8. concentrationconcentrated in vacuo

ORD record

ord-a2e58f9097404807a2c32136fffcd4a6

Source dataset

uspto-grants-2007_04

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07199135B2