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

HRID 1433169Notes

Reaction equation

HRID 1433169 reaction equation
C([C@H]1COC(=O)N1[C:14](=[O:31])[C@@H:15]([C:24]1([OH:30])[CH2:29][CH2:28][CH2:27][CH2:26][CH2:25]1)[C:16]1[CH:21]=[CH:20][C:19]([O:22][CH3:23])=[CH:18][CH:17]=1)C1C=CC=CC=1.[O:32]1CCCC1.O.OO.O.[OH-].[Li+]>O.O1CCCC1>[OH:30][C:24]1([C@@H:15]([C:16]2[CH:17]=[CH:18][C:19]([O:22][CH3:23])=[CH:20][CH:21]=2)[C:14]([OH:31])=[O:32])[CH2:25][CH2:26][CH2:27][CH2:28][CH2:29]1

Participants

7

Reactant 4

HCID 784Hydrogen PeroxideHCID 168937Lithium hydroxide, monohydrateHCID 21881883Oxolane--water (1/1)HCID 24777857(4S)-4-benzyl-3-[(2R)-2-(1-hydroxycyclohexyl)-2-(4-methoxyphenyl)acetyl]-1,3-oxazolidin-2-one

Product 1

HCID 14226999(2R)-(1-hydroxycyclohexyl)-2-(4-methoxyphenyl)acetic acidYield 89%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent

Procedure

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):

Workup

  1. customwas evaporated in vacuo
  2. additionthe aqueous layer was treated with a 2 N aqueous solution of sodium hydroxide (5 mL)
  3. extractionThe aqueous layer was extracted with ethyl acetate (2×15 mL)
  4. extractionThe product was extracted with ethyl acetate (3×50 mL)
  5. dry with materialthe combined organic extracts were dried over magnesium sulfate
  6. concentrationconcentrated
  7. customto yield a white solid which
  8. customwas recrystallized from ethyl acetate/hexane

Sources & evidence

ORD record
ord-c56d8b70c43542e29e03a445929b3f76
Source dataset
uspto-grants-2009_11
Patent number
US07612210B2

Reaction notes

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