Dimethylformamide → 8-(1-t-Butyloxycarbonyl-1,2,5,6-tetrahydropyridin-4-yl)isoquinoline

HRID 1371516Notes

Reaction equation

HRID 1371516 reaction equation
Br[C:2]1[CH:3]=[CH:4][CH:5]=[C:6]2[C:11]=1[CH:10]=[N:9][CH:8]=[CH:7]2.[C:12](=[O:15])([O-])[O-:13].[K+].[K+].[CH3:18][N:19]([CH:21]=O)C>C(Cl)Cl.[CH-]1C=C(P(C2C=CC=CC=2)C2C=CC=CC=2)C=C1.[CH-]1C=C(P(C2C=CC=CC=2)C2C=CC=CC=2)C=C1.Cl[Pd]Cl.[Fe+2]>[C:6]([O:13][C:12]([N:19]1[CH2:21][CH2:4][C:3]([C:2]2[CH:3]=[CH:4][CH:5]=[C:6]3[C:11]=2[CH:10]=[N:9][CH:8]=[CH:7]3)=[CH:2][CH2:18]1)=[O:15])([CH3:11])([CH3:7])[CH3:5]

Participants

6

Reactant 3

HCID 6228DimethylformamideHCID 11430Potassium CarbonateHCID 98591348-Bromoisoquinoline

Product 1

HCID 210709528-(1-t-Butyloxycarbonyl-1,2,5,6-tetrahydropyridin-4-yl)isoquinolineYield 73%

Reagents, catalysts & solvents 2

HCID 44119782Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)CatalystHCID 6344DichloromethaneSolvent

Conditions

Temperature
90 °C

Procedure

8-Bromoisoquinoline (300 mg, 1.44 mmol) is dissolved in DMF (8.7 mL). To the solution is added Boc-piperidine boronic ester (405 mg, 1.31 mmol), dichloro(1,1′-bis(diphenylphosphino)ferrocene)palladium (II) dichloromethane adduct (58 mg, 0.079 mmol) and potassium carbonate (544 mg, 3.93 mmol). The mixture is heated to about 90° C. overnight and cooled, which is then diluted with DCM and filtered through celite. The filtrate is concentrated under vacuum to remove DCM and partitioned between EtOAc (100 mL), hexanes (100 mL) and water (100 mL). The organic fraction is concentrated and chromatographed on silica gel to give about 298 mg of 8-(1-t-butyloxycarbonyl-1,2,5,6-tetrahydropyridin-4-yl)isoquinoline (73%). EIS-MS 311.2 M+1

Workup

  1. temperaturecooled
  2. filtrationfiltered through celite
  3. concentrationThe filtrate is concentrated under vacuum
  4. customto remove DCM
  5. custompartitioned between EtOAc (100 mL), hexanes (100 mL) and water (100 mL)
  6. concentrationThe organic fraction is concentrated
  7. customchromatographed on silica gel

Sources & evidence

ORD record
ord-d00ee3b12e2e4e569ffb7cb9d556b86b
Source dataset
uspto-grants-2007_01
Patent number
US07157463B2

Reaction notes

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