1,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine) → (R)-t-butyl 2-((t-butyldimethylsilyloxy)methyl)-4-(6-chloropyridin-3-yl)piperazine-1-carboxylate

HRID 876013

Reaktionsgleichung

Reaktionsgleichung von HRID 876013
[Si:1]([O:8][CH2:9][C@H:10]1[CH2:15][NH:14][CH2:13][CH2:12][N:11]1[C:16]([O:18][C:19]([CH3:22])([CH3:21])[CH3:20])=[O:17])([C:4]([CH3:7])([CH3:6])[CH3:5])([CH3:3])[CH3:2].Br[C:24]1[CH:25]=[CH:26][C:27]([Cl:30])=[N:28][CH:29]=1.C1(P(C2C=CC=CC=2)C2C3OC4C(=CC=CC=4P(C4C=CC=CC=4)C4C=CC=CC=4)C(C)(C)C=3C=CC=2)C=CC=CC=1.CC(C)([O-])C.[Na+]>C1(C)C=CC=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.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd]>[Si:1]([O:8][CH2:9][C@H:10]1[CH2:15][N:14]([C:24]2[CH:29]=[N:28][C:27]([Cl:30])=[CH:26][CH:25]=2)[CH2:13][CH2:12][N:11]1[C:16]([O:18][C:19]([CH3:22])([CH3:21])[CH3:20])=[O:17])([C:4]([CH3:7])([CH3:5])[CH3:6])([CH3:3])[CH3:2]

Komponenten

7

Edukt 4

HCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)HCID 27344145-Bromo-2-chloropyridineHCID 23676156Sodium t-butoxideHCID 58299667(R)-t-Butyl 2-((t-butyldimethylsilyloxy)methyl)piperazine-1-carboxylate

Produkt 1

HCID 86654440(R)-t-butyl 2-((t-butyldimethylsilyloxy)methyl)-4-(6-chloropyridin-3-yl)piperazine-1-carboxylateAusbeute 48 %

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 9811564Bis(dibenzylideneacetone)palladiumKatalysatorHCID 1140TolueneLösungsmittel

Reaktionsbedingungen

Temperatur
80 °C

Versuchsvorschrift

Compound 308 (361 mg, 1091 μmol), 5-bromo-2-chloropyridine (200 mg, 1039 μmol), Tris(dibenzylideneacetone)dipalladium (0) (71.4 mg, 77.9 μmol), 4,5-bis(diphenylphosphino)-9,9-dimethyl-9H-xanthene (90.2 mg, 156 μmol), and sodium t-butoxide (200 mg, 2079 μmol) were taken up in toluene (5 mL). The reaction was purged with argon and heated at 80° C. for 5 hours. The resulting solution was added to aqueous K2CO3 (10%, 30 mL) and extracted with dichloromethane+10% methanol (3×30 mL). The combined organics were dried (MgSO4) and evaporated to give an orange tar. Silica gel chromatography (gradient elution hexanes/0-20% ethyl acetate) afforded compound 309 as a pale yellow oil (219 mg, 48%).

Aufarbeitung

  1. customThe reaction was purged with argon
  2. additionThe resulting solution was added to aqueous K2CO3 (10%, 30 mL)
  3. extractionextracted with dichloromethane+10% methanol (3×30 mL)
  4. dry with materialThe combined organics were dried (MgSO4)
  5. customevaporated
  6. customto give an orange tar
  7. washSilica gel chromatography (gradient elution hexanes/0-20% ethyl acetate)

Quellen und Nachweise

ORD-Eintrag
ord-fde823539bd143b3aaa12a80f2da9c85
Quelldatensatz
uspto-grants-2015_03
Patentnummer
US08980903B2

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