Water → 1-(Tert-butoxycarbonyl)-4-[2,6-difluoro-4-(benzyloxycarbonyl)aminophenyl]piperazine

HRID 266709

Reaktionsgleichung

Reaktionsgleichung von HRID 266709
[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][N:11]([C:14]2[C:19]([F:20])=[CH:18][C:17]([N+:21]([O-])=O)=[CH:16][C:15]=2[F:24])[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].C([O-])=O.[NH4+].[CH3:29][CH2:30][O:31][C:32](C)=[O:33].O>C1COCC1.CO.[Pd]>[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][N:11]([C:14]2[C:19]([F:20])=[CH:18][C:17]([NH:21][C:32]([O:31][CH2:30][C:29]3[CH:18]=[CH:19][CH:14]=[CH:15][CH:16]=3)=[O:33])=[CH:16][C:15]=2[F:24])[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2]

Komponenten

7

Edukt 4

HCID 962WaterHCID 8857Ethyl AcetateHCID 2723923Ammonium formateHCID 214626024-(2,6-Difluoro-4-nitro-phenyl)-piperazine-1-carboxylic acid tert-butyl ester

Produkt 1

HCID 214626171-(Tert-butoxycarbonyl)-4-[2,6-difluoro-4-(benzyloxycarbonyl)aminophenyl]piperazineAusbeute 67 %

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 23938PalladiumKatalysatorHCID 21899815MeOH tetrahydrofuranLösungsmittel

Versuchsvorschrift

The 1-(tert-butoxycarbonyl)-4-(2,6-difluoro-4-nitrophenyl)piperazine (44.7 g, 130 mmol) was dissolved in 20% THF/MeOH (600 mL) in a 2 L flask. Ammonium formate (41 g, 651 mmol) was added portionwise, followed by 10% Pd-C (1.12 g, 2.5 weight %), with cooling in an ice bath. When the addition was completed the ice bath was removed. The flask became slightly warm, and the yellow color disappeared. The reaction mixture was filtered through Celite (washing the filter cake with 500 mL MeOH). The filtrate was concentrated under reduced pressure to give a solid which was then treated with 1 L EtOAc and 500 mL H2O. The layers were separated and then the organic layer was washed again with H2O (500 mL) and once with brine (500 mL). The aqueous portions were back-extracted with more EtOAc (2×300 mL). The combined organic extracts were dried over anhydrous Na2SO4, filtered and concentrated to yield a yellow solid. The crude material was recrystallized from hot EtOAc/hexane to afford 39.11 g (67%) of the title compound as a pale yellow crystalline solid with mp 171°-172° C.

Aufarbeitung

  1. temperaturewith cooling in an ice bath
  2. additionWhen the addition
  3. customwas removed
  4. temperatureThe flask became slightly warm
  5. filtrationThe reaction mixture was filtered through Celite (
  6. washwashing the filter cake with 500 mL MeOH)
  7. concentrationThe filtrate was concentrated under reduced pressure
  8. customto give a solid which
  9. customThe layers were separated
  10. washthe organic layer was washed again with H2O (500 mL) and once with brine (500 mL)
  11. extractionThe aqueous portions were back-extracted with more EtOAc (2×300 mL)
  12. dry with materialThe combined organic extracts were dried over anhydrous Na2SO4
  13. filtrationfiltered
  14. concentrationconcentrated
  15. customto yield a yellow solid
  16. customThe crude material was recrystallized from hot EtOAc/hexane

Quellen und Nachweise

ORD-Eintrag
ord-16d68f99d1b44a39a01b69459355caff
Quelldatensatz
uspto-grants-1997_07
Patentnummer
US05652238

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