Ketoprofen → (R)-Ketoprofen

HRID 1489392Notes

Reaction equation

HRID 1489392 reaction equation
C1(C)C=CC=CC=1.[OH:8][C:9]([C@@H:11]([C:13]1[CH:26]=[CH:25][CH:24]=[C:15]([C:16]([C:18]2[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=2)=[O:17])[CH:14]=1)[CH3:12])=[O:10].OC(C(C1C=CC=C(C(C2C=CC=CC=2)=O)C=1)C)=O.[OH-].[Na+]>O>[OH:10][C:9]([C@@H:11]([C:13]1[CH:26]=[CH:25][CH:24]=[C:15]([C:16]([C:18]2[CH:19]=[CH:20][CH:21]=[CH:22][CH:23]=2)=[O:17])[CH:14]=1)[CH3:12])=[O:8]

Participants

5

Reactant 3

HCID 3825KetoprofenHCID 14798Sodium HydroxideHCID 131720248HCID 131720248, compound

Product 1

HCID 180540(R)-Ketoprofen

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Conditions

Temperature
115 °C

Procedure

To 468 g of a toluene/(R)-ketoprofen (63% EE) solution containing 94 g of ketoprofen, 671 g of deionized water was added followed by 153 g of 50% NaOH. The phases were mixed and then separated. The aqueous phase was heated to 115° C. (under pressure) and maintained at this temperature for 3 hours. The solution was then cooled to room temperature and 842 g of toluene were added, followed by 103 g of concentrated sulfuric acid. The phases were mixed and the aqueous phase decanted. After decolorization with activated carbon, the organic phase was concentrated to 25% ketoprofen concentration. The concentrate was cooled to 0° C. and kept at this temperature for 5 hours. The solids were filtered, washed with toluene, and dried under vacuum. The weight of the racemized ketoprofen was 62 g and the enantiomeric excess was 1.4% (R)-ketoprofen.

Workup

  1. additionwas added
  2. additionThe phases were mixed
  3. customseparated
  4. temperaturemaintained at this temperature for 3 hours
  5. temperatureThe solution was then cooled to room temperature
  6. addition842 g of toluene were added
  7. additionThe phases were mixed
  8. customthe aqueous phase decanted
  9. concentrationAfter decolorization with activated carbon, the organic phase was concentrated to 25% ketoprofen concentration
  10. temperatureThe concentrate was cooled to 0° C.
  11. filtrationThe solids were filtered
  12. washwashed with toluene
  13. customdried under vacuum

Sources & evidence

ORD record
ord-b4efa925645741c7a986a4c18787b5ac
Source dataset
uspto-grants-1997_10
Patent number
US05677469

Reaction notes

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