Hydrogen Peroxide → (2R)-(1-hydroxycyclohexyl)-2-(4-methoxyphenyl)acetic acid

Participants

Reaction Steps

A solution of (4S)-4-benzyl-3-[(2R)-2-(1-hydroxycyclohexyl)-2-(4-methoxyphenyl)-acetyl]-1,3-oxazolidin-2-one (1.02 g, 2.4 mmol) in 4:1 tetrahydrofuran/water (25 mL) at 0° C. was treated dropwise with a premixed solution of hydrogen peroxide (50% in water, 0.59 mL, 9.6 mmol) and lithium hydroxide monohydrate (115 mg, 4.8 mmol) in water (1 mL). The reaction was stirred at 25° C. for 2 h after which time the tetrahydrofuran was evaporated in vacuo and the aqueous layer was treated with a 2 N aqueous solution of sodium hydroxide (5 mL). The aqueous layer was extracted with ethyl acetate (2×15 mL) followed by methylene chloride (2×15 mL) and the aqueous layer was acidified to pH=2 with a 2 N aqueous solution of hydrochloric acid. The product was extracted with ethyl acetate (3×50 mL) and the combined organic extracts were dried over magnesium sulfate and concentrated to yield a white solid which was recrystallized from ethyl acetate/hexane to yield 565 mg (89%) (2R)-(1-hydroxycyclohexyl)-2-(4-methoxyphenyl)acetic acid. MS (ESI) m/z 247; MS (ESI) m/z 263; [α]D25=+71° (c=0.010 g/mL, EtOH); HRMS: calcd for C15H2OO4+NH4+, 282.16998; found (ESI-FT/MS, [M+NH4]1+), 282.1706; enantiomeric excess >99%. The enantiomeric purity was determined, compared to the racemate, under the following Supercritical Fluid Chromatography conditions using Analytical Supercritical Fluid Chromatography (Berger Instruments, Inc. Newark, Del. USA):

Provenance & Evidence