Water → HCID 49793374, compound

HRID 2122059Notes

Reaction equation

HRID 2122059 reaction equation
C([N:8]1[C:12](=[O:13])[CH:11]=[CH:10][C:9]1=[O:14])C1C=CC=CC=1.C(OCC)(=[O:17])C.I([O-])(=O)(=O)=O.[Na+].[OH2:27]>C(#N)C.O.[Ru](Cl)(Cl)Cl>[OH:27][C@H:10]1[C@@H:11]([OH:17])[C:12](=[O:13])[NH:8][C:9]1=[O:14]

Participants

7

Reactant 4

HCID 962WaterHCID 8857Ethyl AcetateHCID 74204BenzylmaleimideHCID 23667635Sodium periodate

Product 1

HCID 49793374HCID 49793374, compoundYield 71%

Reagents, catalysts & solvents 2

HCID 6093376Ruthenium trichloride hydrateCatalystHCID 6342AcetonitrileSolvent

Conditions

Temperature
5 °C

Procedure

A solution of N-benzylmaleimide (50.0 kg), in 125 L of acetonitrile and 859 L of ethyl acetate was combined with an aqueous mixture of 0.499 kg of ruthenium (III) chloride hydrate in 352 L of water, and the resulting reaction mixture was cooled to about 5° C. Sodium periodate (74.4 kg) was added with stirring to the reaction solution in small portions, while maintaining the reaction temperature between 3° C. and 5° C. Once the addition was complete, the reaction was quenched with an aqueous solution of sodium thiosulfate (45 kg) in 38 L of water, and the resulting slurry was granulated for about 20 minutes. The inorganic salts were removed by suction filtration, and the filter cake was washed with ethyl acetate. The combined filtrates were washed with water and allowed to settle. The aqueous layer was extracted with ethyl acetate and the product-rich organic layers were combined and washed with a solution of 8 kg of sodium chloride in 72 L of water. The organic extracts were concentrated by atmospheric distillation at a temperature of about 75° C., cooled to room temperature, and allowed to granulate for 2 to 4 hours. Hexanes (360 L) was added to the cooled (5° C. to 15° C.) slurry and granulation was continued for about 1 hour. The precipitated solids were collected by suction filtration, washed well with ethyl acetate followed by hexanes, and then dried in vacuo at a temperature of about 40° C. to about 45° C. to provide the title compound (42.0 kg, 71% yield) as a white solid.

Workup

  1. customthe resulting reaction mixture
  2. temperaturewhile maintaining the reaction temperature between 3° C. and 5° C
  3. additionOnce the addition
  4. customthe reaction was quenched with an aqueous solution of sodium thiosulfate (45 kg) in 38 L of water
  5. customThe inorganic salts were removed by suction filtration
  6. washthe filter cake was washed with ethyl acetate
  7. washThe combined filtrates were washed with water
  8. extractionThe aqueous layer was extracted with ethyl acetate
  9. washwashed with a solution of 8 kg of sodium chloride in 72 L of water
  10. concentrationThe organic extracts were concentrated by atmospheric distillation at a temperature of about 75° C.
  11. temperaturecooled to room temperature
  12. waitto granulate for 2 to 4 hours
  13. additionHexanes (360 L) was added to the
  14. temperaturecooled (5° C. to 15° C.) slurry and granulation
  15. waitwas continued for about 1 hour
  16. filtrationThe precipitated solids were collected by suction filtration
  17. washwashed well with ethyl acetate
  18. customdried in vacuo at a temperature of about 40° C. to about 45° C.

Sources & evidence

ORD record
ord-2535e930764b4b3ab6859d668648f230
Source dataset
uspto-grants-2004_02
Patent number
US06696574B2

Reaction notes

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