Hydrogen Peroxide → (S)-3-(4-hydroxyphenyl)-2-(4-methylphenoxy)propionic acid

HRID 1268949Notes

Reaction equation

HRID 1268949 reaction equation
C([C@H]1COC(=O)N1[C:14](=[O:32])[C@@H:15]([O:24][C:25]1[CH:30]=[CH:29][C:28]([CH3:31])=[CH:27][CH:26]=1)[CH2:16][C:17]1[CH:22]=[CH:21][C:20]([OH:23])=[CH:19][CH:18]=1)C1C=CC=CC=1.[OH-].[Li+].OO.S(S([O-])=O)([O-])=[O:38].[Na+].[Na+]>CO>[OH:23][C:20]1[CH:19]=[CH:18][C:17]([CH2:16][C@H:15]([O:24][C:25]2[CH:26]=[CH:27][C:28]([CH3:31])=[CH:29][CH:30]=2)[C:14]([OH:32])=[O:38])=[CH:22][CH:21]=1

Participants

6

Reactant 4

HCID 784Hydrogen PeroxideHCID 3939Lithium HydroxideHCID 24489Sodium DithioniteHCID 69504567(S)-4-Benzyl-3-[(S)-3-(4-hydroxyphenyl)-2-(4-methylphenoxy)propionyl]oxazolidin-2-one

Product 1

HCID 69504559(S)-3-(4-hydroxyphenyl)-2-(4-methylphenoxy)propionic acidYield 82.4%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

To a suspension of (S)-4-benzyl-3-[(S)-3-(4-hydroxyphenyl)-2-(4-methylphenoxy)propionyl]oxazolidin-2-one (6.50 g) obtained from Reference example 20(d) in methanol (80 ml) was added dropwise a mixed solution of an aqueous solution of lithium hydroxide (1N, 37.7 ml) and an aqueous solution of hydrogen peroxide (31%, 4.14 ml). The reaction solution was stirred for 1 hour at room temperature, then an aqueous solution (20 ml) of sodium hydrosulfite (6.56 g) was added thereto followed by stirring for 1 hour, and the resulting reaction solution was concentrated under reduced pressure. To the residue was added an aqueous solution of sodium hydroxide (1N), then the resulting alkaline solution was washed with dichloromethane and acidified by addition of hydrochloric acid. Ethyl acetate was added thereto, and the resulting solution was stirred and partitioned between ethyl acetate and water. The separated ethyl acetate layer was dried over anhydrous magnesium sulfate, and concentrated under reduced pressure. The residue was crystallized by addition of isopropyl ether and hexane to yield (S)-3-(4-hydroxyphenyl)-2-(4-methylphenoxy)propionic acid (3.38 g) as a white powder.

Workup

  1. stirringby stirring for 1 hour
  2. customthe resulting reaction solution
  3. concentrationwas concentrated under reduced pressure
  4. additionTo the residue was added an aqueous solution of sodium hydroxide (1N)
  5. washthe resulting alkaline solution was washed with dichloromethane
  6. additionacidified by addition of hydrochloric acid
  7. additionEthyl acetate was added
  8. stirringthe resulting solution was stirred
  9. custompartitioned between ethyl acetate and water
  10. dry with materialThe separated ethyl acetate layer was dried over anhydrous magnesium sulfate
  11. concentrationconcentrated under reduced pressure
  12. customThe residue was crystallized by addition of isopropyl ether and hexane

Sources & evidence

ORD record
ord-ab281fd1f4864d35bde3cd6ad27a7231
Source dataset
uspto-grants-2007_04
Patent number
US07199139B2

Reaction notes

Loading…