Cyclopropylboronic acid → 6-cyclopropyl-3,4-dihydro-2H-isoquinolin-1-one

HRID 2069803Notes

Reaction equation

HRID 2069803 reaction equation
Br[C:2]1[CH:3]=[C:4]2[C:9](=[CH:10][CH:11]=1)[C:8](=[O:12])[NH:7][CH2:6][CH2:5]2.[CH:13]1(B(O)O)[CH2:15][CH2:14]1>C1(C)C=CC=CC=1.O.CC([O-])=O.CC([O-])=O.[Pd+2].C1(P(C2CCCCC2)C2CCCCC2)CCCCC1>[CH:13]1([C:2]2[CH:3]=[C:4]3[C:9](=[CH:10][CH:11]=2)[C:8](=[O:12])[NH:7][CH2:6][CH2:5]3)[CH2:15][CH2:14]1

Participants

7

Reactant 2

HCID 2760897Cyclopropylboronic acidHCID 218654506-Bromo-3,4-dihydro-2H-isoquinolin-1-one

Product 1

HCID 574241176-cyclopropyl-3,4-dihydro-2H-isoquinolin-1-oneYield 97.2%

Reagents, catalysts & solvents 4

HCID 75806TricyclohexylphosphineCatalystHCID 167845palladium(II) acetateCatalystHCID 962WaterSolventHCID 1140TolueneSolvent

Conditions

Temperature
100 °C

Procedure

To a round bottomed flask charged with 6-Bromo-3,4-dihydro-2H-isoquinolin-1-one (16.9 g, 74.7 mmol), cyclopropylboronic acid (9.45 g, 1.5 equiv), tricyclohexylphosphine (1.04 mg, 0.025 equiv), and K3PO4 hexahydrate (50 g, 2 equiv) in toluene (210 mL) and H2O (15 mL) was added Pd(OAc)2 (100 mg, 0.05 equiv). The combined mixture was heated for 4 h at 100° C. The reaction mixture was cooled, filtered and washed with toluene. The organic phase was partitioned and washed with water and brine, dried over Na2SO4, filtered and concentrated to an oil. Addition of hexanes produced 6-Cyclopropyl-3,4-dihydro-2H-isoquinolin-1-one as a tan solid (13.6 g). MS (ESI) 187.1 (M+H)+.

Workup

  1. temperatureThe reaction mixture was cooled
  2. filtrationfiltered
  3. washwashed with toluene
  4. customThe organic phase was partitioned
  5. washwashed with water and brine
  6. dry with materialdried over Na2SO4
  7. filtrationfiltered
  8. concentrationconcentrated to an oil
  9. additionAddition of hexanes

Sources & evidence

ORD record
ord-b52d7ef86b4a4892a9064892d2b42a2a
Source dataset
uspto-grants-2012_10
Patent number
US08299077B2

Reaction notes

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