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

HRID 2066102Notes

Reaction equation

HRID 2066102 reaction equation
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]

Participants

6

Reactant 2

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

Product 1

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

Reagents, catalysts & solvents 3

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

Conditions

Temperature
120 °C

Procedure

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).

Workup

  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)

Sources & evidence

ORD record
ord-782d4d370b3c45ce8ab7255489fd69ac
Source dataset
uspto-grants-2012_10
Patent number
US08288388B2

Reaction notes

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