Potassium Hydroxide → Bicalutamide

HRID 719849

Reaktionsgleichung

Reaktionsgleichung von HRID 719849
[C:1]([C:3]1[CH:23]=[CH:22][C:6]([NH:7][C:8](=[O:21])[C:9]([OH:20])([CH3:19])[CH2:10][S:11][C:12]2[CH:17]=[CH:16][C:15]([F:18])=[CH:14][CH:13]=2)=[CH:5][C:4]=1[C:24]([F:27])([F:26])[F:25])#[N:2].C1C=C(C(O)=[O:35])C(C(OO)=O)=CC=1.[OH-:41].[K+]>C(OCC)(=O)C>[C:1]([C:3]1[CH:23]=[CH:22][C:6]([NH:7][C:8](=[O:21])[C:9]([OH:20])([CH3:19])[CH2:10][S:11]([C:12]2[CH:13]=[CH:14][C:15]([F:18])=[CH:16][CH:17]=2)(=[O:35])=[O:41])=[CH:5][C:4]=1[C:24]([F:27])([F:25])[F:26])#[N:2]

Komponenten

5

Edukt 3

HCID 14797Potassium HydroxideHCID 75329Monoperoxyphthalic acidHCID 9800987Bicalutamide sulfide

Produkt 1

HCID 2375BicalutamideAusbeute 91,2 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 8857Ethyl AcetateLösungsmittel2×

Reaktionsbedingungen

Temperatur
60 °C

Versuchsvorschrift

4′-Cyano-3-(4-fluorophenylthio)-2-hydroxy-2-methyl-3′-trifluoromethylpropionanilide (12.20 g, 30.6 mmol) and ethyl acetate (20 ml) were successively charged in a 200 ml four-neck flask, and the mixture was stirred under ice-cooling (2° C.–7° C.). A solution of mono-perphthalic acid in ethyl acetate (166.58 g, net 22.31 g, 122.5 mmol) was dropwise added at not higher than 10° C., and the mixture was stirred for 1 hr. A 20% KOH solution (117.5 g) was dropwise added thereto and the mixture was partitioned. The aqueous layer was extracted with ethyl acetate (30 ml). The combined organic layer was washed with a solution of sodium pyrosulfite (3.0 g) dissolved in deionized water (30 ml), dried over magnesium sulfate and concentrated under reduced pressure. Ethyl acetate (66 ml) was added to the residue and the mixture was heated to 60° C. n-Heptane (40 ml) was added dropwise at a temperature of 60° C.–65° C. over 40 min. After the completion of the dropwise addition, the mixture was allowed to cool to room temperature (about 20° C.–25° C.) and filtrated to give 4′-cyano-3-[(4-fluorophenyl)sulfonyl]-2-hydroxy-2-methyl-3′-trifluoromethylpropionanilide (12.24 g, yield 91.2%). Purity 99.97%.

Aufarbeitung

  1. temperaturecooling (2° C.–7° C.)
  2. stirringthe mixture was stirred for 1 hr
  3. customthe mixture was partitioned
  4. extractionThe aqueous layer was extracted with ethyl acetate (30 ml)
  5. washThe combined organic layer was washed with a solution of sodium pyrosulfite (3.0 g)
  6. dissolutiondissolved in deionized water (30 ml)
  7. dry with materialdried over magnesium sulfate
  8. concentrationconcentrated under reduced pressure
  9. additionEthyl acetate (66 ml) was added to the residue
  10. additionwas added dropwise at a temperature of 60° C.–65° C. over 40 min
  11. additionAfter the completion of the dropwise addition
  12. temperatureto cool to room temperature (about 20° C.–25° C.)
  13. filtrationfiltrated

Quellen und Nachweise

ORD-Eintrag
ord-083c17ce35704e82a628968ade3db0a5
Quelldatensatz
uspto-grants-2006_11
Patentnummer
US07132560B2

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