Cesium carbonate → tert-Butyl 4-(isoquinolin-3-yl)piperazine-1-carboxylate

HRID 1775328Notes

Reaction equation

HRID 1775328 reaction equation
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.C(=O)([O-])[O-].[Cs+].[Cs+].Cl[C:54]1[CH:63]=[CH:62][C:61]2[C:56](=[CH:57][CH:58]=[CH:59][CH:60]=2)[N:55]=1.[N:64]1([C:70]([O:72][C:73]([CH3:76])([CH3:75])[CH3:74])=[O:71])[CH2:69][CH2:68][NH:67][CH2:66][CH2:65]1>O1CCOCC1.C(OCC)(=O)C.C([O-])(=O)C.[Pd+2].C([O-])(=O)C>[CH:56]1[C:61]2[C:62](=[CH:57][CH:58]=[CH:59][CH:60]=2)[CH:63]=[C:54]([N:67]2[CH2:66][CH2:65][N:64]([C:70]([O:72][C:73]([CH3:76])([CH3:75])[CH3:74])=[O:71])[CH2:69][CH2:68]2)[N:55]=1

Participants

8

Reactant 4

HCID 10796Cesium carbonateHCID 119282-ChloroquinolineHCID 143452tert-Butyl piperazine-1-carboxylateHCID 634876Binap, (A+-)-

Product 1

HCID 57690803tert-Butyl 4-(isoquinolin-3-yl)piperazine-1-carboxylateYield 32.1%

Reagents, catalysts & solvents 3

HCID 167845palladium(II) acetateCatalystHCID 8857Ethyl AcetateSolventHCID 312751,4-DioxaneSolvent2×

Conditions

Temperature
110 °C

Procedure

Palladium acetate (63 mg, 0.8 mmol), BINAP (250 mg, 0.4 mmol) and caesium carbonate (1.3 g, 4 mmol) were suspended in anhydrous 1,4-dioxane (9 ml) under an argon atmosphere and sonicated for 40 minutes. 2-Chloroquinoline (343 mg, 2 mmol) and tert-butyl piperazine-1-carboxylate (373 mg, 2 mmol) were dissolved in anhydrous 1,4-dioxane (3 ml) and the resulting solution was added to the catalyst-containing mixture. The resulting mixture was stirred at 110° C. for three hours, cooled to room temperature and diluted with ethyl acetate. The solids were removed by centrifugation and decantation, the supernatant was evaporated to dryness under reduced pressure and the resulting residue was dissolved in DCM and filtered through a silica column. The product was eluted with a mixture of DCM and diethylether. After removal of the solvent under reduced pressure, 201 mg of a solid were obtained (0.64 mmol, 32%) MS (ESI) m/z=314.2 [M+1]+.

Workup

  1. customsonicated for 40 minutes
  2. additionthe resulting solution was added to the catalyst-containing mixture
  3. temperaturecooled to room temperature
  4. customThe solids were removed by centrifugation and decantation
  5. customthe supernatant was evaporated to dryness under reduced pressure
  6. dissolutionthe resulting residue was dissolved in DCM
  7. filtrationfiltered through a silica column
  8. washThe product was eluted with a mixture of DCM and diethylether
  9. customAfter removal of the solvent under reduced pressure

Sources & evidence

ORD record
ord-0e3b77a5e92a44ed9a5efcc90f65898c
Source dataset
uspto-grants-2016_02
Patent number
US09260441B2

Reaction notes

Loading…