Piperazine → HCID 18436771, Verbindung

HRID 456433Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 456433
[C:1]([N:8]1[CH2:13][CH2:12][CH:11]([O:14][C:15]2[CH:20]=[CH:19][CH:18]=[CH:17][C:16]=2Br)[CH2:10][CH2:9]1)([O:3][C:4]([CH3:7])([CH3:6])[CH3:5])=[O:2].[NH:22]1[CH2:27][CH2:26][NH:25][CH2:24][CH2:23]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([O-])(C)C.[Na+]>C1(C)C=CC=CC=1.CCOC(C)=O.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]>[C:1]([N:8]1[CH2:13][CH2:12][CH:11]([O:14][C:15]2[CH:20]=[CH:19][CH:18]=[CH:17][C:16]=2[N:22]2[CH2:27][CH2:26][NH:25][CH2:24][CH2:23]2)[CH2:10][CH2:9]1)([O:3][C:4]([CH3:7])([CH3:6])[CH3:5])=[O:2]

Komponenten

8

Edukt 4

HCID 4837PiperazineHCID 634876Binap, (A+-)-HCID 16731688HCID 16731688, VerbindungHCID 23676156Sodium t-butoxide

Produkt 1

HCID 18436771HCID 18436771, VerbindungAusbeute 93 %

Reagenzien, Katalysatoren, Lösungsmittel 3

HCID 9811564Bis(dibenzylideneacetone)palladiumKatalysatorHCID 1140TolueneLösungsmittelHCID 8857Ethyl AcetateLösungsmittel

Reaktionsbedingungen

Temperatur
95 °C

Versuchsvorschrift

To a solution of N-boc-4-(2-bromo-phenoxy)-piperidine (13.4 g, 39.6 mmol, 1.0 eq.), piperazine (9.73 g, 113 mmol, 3.0 eq.), Pd2dba3 (1.72 g, 1.88 mmol, 0.05 eq.), BINAP (3.5 g, 5.65 mmol, 0.15 eq.) in toluene (150 mL) was added NaOtBu (5.1 g, 52.6 mmol, 1.4 eq.). The mixture was heated to 95° C. and stirred at that temperature overnight. The slurry was diluted with EtOAc and filtered through a pad of celite. The filtrate was concentrated and purified by ion exchange (SCX, 10 g) column. Further purification by flash chromatography (250 g SiO2, 40 ml/min, linear gradient 0–10% 2.0 M NH3 in MeOH/CH2Cl2 for 20 minutes and 10% 2.0 M NH3 in MeOH/CH2Cl2 for 73 minutes) afforded the final compound (12.65 g, 93%). LRMS (electrospray): 362.7 (M+1).

Aufarbeitung

  1. filtrationfiltered through a pad of celite
  2. concentrationThe filtrate was concentrated
  3. custompurified by ion exchange (SCX, 10 g) column
  4. customFurther purification by flash chromatography (250 g SiO2, 40 ml/min, linear gradient 0–10% 2.0 M NH3 in MeOH/CH2Cl2 for 20 minutes and 10% 2.0 M NH3 in MeOH/CH2Cl2 for 73 minutes)

Quellen und Nachweise

ORD-Eintrag
ord-b945508cc3f346f29dc68afcd79b546d
Quelldatensatz
uspto-grants-2007_03
Patentnummer
US07186715B2

Notizen zur Reaktion

Wird geladen…