tert-Butyl piperazine-1-carboxylate → tert-Butyl 4-(isoquinolin-5-yl)piperazine-1-carboxylate

HRID 459830Notes

Reaction equation

HRID 459830 reaction equation
Br[C:2]1[CH:11]=[CH:10][CH:9]=[C:8]2[C:3]=1[CH:4]=[CH:5][N:6]=[CH:7]2.C1(P(C2C=CC=CC=2)C2C=CC3C(=CC=CC=3)C=2C2C3C(=CC=CC=3)C=CC=2P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.[C:58]([O:62][C:63]([N:65]1[CH2:70][CH2:69][NH:68][CH2:67][CH2:66]1)=[O:64])([CH3:61])([CH3:60])[CH3:59].CC(C)([O-])C.[Na+]>C1(C)C=CC=CC=1.C(OCC)(=O)C.C([O-])(=O)C.[Pd+2].C([O-])(=O)C>[C:58]([O:62][C:63]([N:65]1[CH2:70][CH2:69][N:68]([C:2]2[CH:11]=[CH:10][CH:9]=[C:8]3[C:3]=2[CH:4]=[CH:5][N:6]=[CH:7]3)[CH2:67][CH2:66]1)=[O:64])([CH3:61])([CH3:59])[CH3:60]

Participants

8

Reactant 4

HCID 143452tert-Butyl piperazine-1-carboxylateHCID 634876Binap, (A+-)-HCID 7364875-BromoisoquinolineHCID 23676156Sodium t-butoxide

Product 1

HCID 21070949tert-Butyl 4-(isoquinolin-5-yl)piperazine-1-carboxylate

Reagents, catalysts & solvents 3

HCID 167845palladium(II) acetateCatalystHCID 1140TolueneSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
100 °C

Procedure

5-Bromoisoquinoline (1.37 g) from Step 1 was dissolved in 10 mL of toluene. To this solution was added palladium acetate (74 mg), rac-2,2′-bis(diphenylphosphino)-1,1′-binaphthyl (205 mg), 1-(tert-butoxycarbonyl)piperazine (1.29 g) and sodium tert-butoxide (885 mg). This reaction mixture was heated to 100° C. for 8 hours and then allowed to cool to room temperature. The cooled reaction mix was diluted with ethyl acetate (EtOAc) and washed with water, and the organic layer was separated, dried over magnesium sulfate (MgSO4), and concentrated in vacuo. The resulting residue was chromatographed to yield 4-isoquinoline-5-yl-piperazine-1-carboxylic acid tert-butyl ester as 1.5 g of a white solid.

Workup

  1. temperatureto cool to room temperature
  2. customThe cooled reaction
  3. additionmix
  4. washwashed with water
  5. customthe organic layer was separated
  6. dry with materialdried over magnesium sulfate (MgSO4)
  7. concentrationconcentrated in vacuo
  8. customThe resulting residue was chromatographed

Sources & evidence

ORD record
ord-61939400dbce484b9a70d39c46e1a9e2
Source dataset
uspto-grants-2007_03
Patent number
US07196088B2

Reaction notes

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