Dimethylformamide → 1,1-dimethylethyl (2R)-4-[(4-cyano-2-methylphenyl)sulfonyl]-2-methyl-1-piperazinecarboxylate

HRID 2066102Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 2066102
Br[C:2]1[CH:7]=[CH:6][C:5]([S:8]([N:11]2[CH2:16][CH2:15][N:14]([C:17]([O:19][C:20]([CH3:23])([CH3:22])[CH3:21])=[O:18])[C@H:13]([CH3:24])[CH2:12]2)(=[O:10])=[O:9])=[C:4]([CH3:25])[CH:3]=1.[CH3:26][N:27](C=O)C>[C-]#N.[C-]#N.[Zn+2].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].C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.[Fe+2]>[C:26]([C:2]1[CH:7]=[CH:6][C:5]([S:8]([N:11]2[CH2:16][CH2:15][N:14]([C:17]([O:19][C:20]([CH3:22])([CH3:23])[CH3:21])=[O:18])[C@H:13]([CH3:24])[CH2:12]2)(=[O:9])=[O:10])=[C:4]([CH3:25])[CH:3]=1)#[N:27]

Komponenten

6

Edukt 2

HCID 6228DimethylformamideHCID 591613521,1-dimethylethyl (2R)-4-[(4-bromo-2-methylphenyl)sulfonyl]-2-methyl-1-piperazinecarboxylate

Produkt 1

HCID 591613281,1-dimethylethyl (2R)-4-[(4-cyano-2-methylphenyl)sulfonyl]-2-methyl-1-piperazinecarboxylate

Reagenzien, Katalysatoren, Lösungsmittel 3

HCID 11186Zinc cyanide (Zn(CN)2)KatalysatorHCID 635956Ferrocene-1,1'-bis-(diphenylphosphine)KatalysatorHCID 9811564Bis(dibenzylideneacetone)palladiumKatalysator

Reaktionsbedingungen

Temperatur
120 °C

Versuchsvorschrift

Ar was bubbled through a solution of 1,1-dimethylethyl (2R)-4-[(4-bromo-2-methylphenyl)sulfonyl]-2-methyl-1-piperazinecarboxylate (may be prepared as described in Description 18) (4.34 g, 10.0 mmol) in dry DMF (40 ml) for 30 min, then Zn(CN)2 (0.647 g, 5.51 mmol), Pd2(dba)3 (0.275 g, 0.300 mmol) and DPPF (0.333 g, 0.601 mmol) were added and the resulting brown solution stirred at 120° C. under Ar for 1 h. The mixture was cooled to room temperature, concentrated under vacuum and the residue partitioned between DCM (100 ml) and water (100 ml). The aqueous layer was extracted with DCM (2×50 ml), then the combined organic layers passed through a hydrophobic frit. Concentration gave a brown residue that was purified by flash chromatography (silica; Flash 40M; linear gradient (8-66%) EtOAc in isohexane) to give the title compound as a viscous pale yellow oil (3.42 g).

Aufarbeitung

  1. temperatureThe mixture was cooled to room temperature
  2. concentrationconcentrated under vacuum
  3. customthe residue partitioned between DCM (100 ml) and water (100 ml)
  4. extractionThe aqueous layer was extracted with DCM (2×50 ml)
  5. concentrationConcentration
  6. customgave a brown residue that
  7. customwas purified by flash chromatography (silica; Flash 40M; linear gradient (8-66%) EtOAc in isohexane)

Quellen und Nachweise

ORD-Eintrag
ord-782d4d370b3c45ce8ab7255489fd69ac
Quelldatensatz
uspto-grants-2012_10
Patentnummer
US08288388B2

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