tert-Butyl piperazine-1-carboxylate → 4-[5-(Piperazin-1-yl)pyrimidin-2-yl]morpholine

HRID 1021239

Reaktionsgleichung

Reaktionsgleichung von HRID 1021239
Br[C:2]1[CH:3]=[N:4][C:5]([N:8]2[CH2:13][CH2:12][O:11][CH2:10][CH2:9]2)=[N:6][CH:7]=1.[N:14]1(C(OC(C)(C)C)=O)[CH2:19][CH2:18][NH:17][CH2:16][CH2:15]1.C1C=CC(P(C2C(C3C(P(C4C=CC=CC=4)C4C=CC=CC=4)=CC=C4C=3C=CC=C4)=C3C(C=CC=C3)=CC=2)C2C=CC=CC=2)=CC=1.CC(C)([O-])C.[K+].Cl.O1CCOCC1>C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd].CCO.C1(C)C=CC=CC=1>[N:14]1([C:2]2[CH:3]=[N:4][C:5]([N:8]3[CH2:13][CH2:12][O:11][CH2:10][CH2:9]3)=[N:6][CH:7]=2)[CH2:19][CH2:18][NH:17][CH2:16][CH2:15]1

Komponenten

9

Edukt 5

HCID 143452tert-Butyl piperazine-1-carboxylateHCID 634876Binap, (A+-)-HCID 51443624-(5-Bromopyrimidin-2-yl)morpholineHCID 204431481,4-Dioxane hydrochlorideHCID 23665647Potassium tert-butoxide

Produkt 1

HCID 866862114-[5-(Piperazin-1-yl)pyrimidin-2-yl]morpholineAusbeute 33,4 %

Reagenzien, Katalysatoren, Lösungsmittel 3

HCID 9811564Bis(dibenzylideneacetone)palladiumKatalysatorHCID 702EthanolLösungsmittelHCID 1140TolueneLösungsmittel

Reaktionsbedingungen

Temperatur
90 °C

Versuchsvorschrift

Under argon atmosphere, 4-(5-bromopyrimidin-2-yl)morpholine (700 mg) and tert-butyl piperazine-1-carboxylate (800 mg) were mixed with toluene (10 ml), and Pd2(dba)3 (130 mg), BINAP (260 mg), and potassium tert-butoxide (500 mg) were added thereto, followed by stirring at 90° C. overnight. The reaction mixture was cooled to room temperature, the reaction mixture was concentrated under reduced pressure, and the residue was purified by silica gel column chromatography (hexane/EtOAc). The purified product thus obtained was mixed with EtOH (10 ml), and 4 M hydrogen chloride/dioxane (7 ml) was added thereto, followed by stirring at room temperature overnight. The reaction mixture was concentrated under reduced pressure, and CHCl3 and a saturated aqueous sodium hydrogen carbonate solution were then added thereto. The organic layer was dried over Na2SO4 and concentrated under reduced pressure. The obtained residue was purified by silica gel column chromatography (CHCl3/MeOH) to obtain 4-[5-(piperazin-1-yl)pyrimidin-2-yl]morpholine (239 mg).

Aufarbeitung

  1. additionwere added
  2. temperatureThe reaction mixture was cooled to room temperature
  3. concentrationthe reaction mixture was concentrated under reduced pressure
  4. customthe residue was purified by silica gel column chromatography (hexane/EtOAc)
  5. customThe purified product thus obtained
  6. additionwas added
  7. stirringby stirring at room temperature overnight
  8. concentrationThe reaction mixture was concentrated under reduced pressure, and CHCl3
  9. additiona saturated aqueous sodium hydrogen carbonate solution were then added
  10. dry with materialThe organic layer was dried over Na2SO4
  11. concentrationconcentrated under reduced pressure
  12. customThe obtained residue was purified by silica gel column chromatography (CHCl3/MeOH)

Quellen und Nachweise

ORD-Eintrag
ord-60547b0803a9417484712e8258466c8b
Quelldatensatz
uspto-grants-2014_05
Patentnummer
US08716470B2

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