Potassium Phosphate, Tribasic → 6-Cyclopropyl-8-fluoro-3,4-dihydroisoquinolin-1(2H)-one
Reaction equation
Br[C:2]1[CH:3]=[C:4]2[C:9](=[C:10]([F:12])[CH:11]=1)[C:8](=[O:13])[NH:7][CH2:6][CH2:5]2.C1(P([CH:27]2[CH2:32][CH2:31]CCC2)C2CCCCC2)CCCCC1.C1(B(O)O)CC1.P([O-])([O-])([O-])=O.[K+].[K+].[K+]>C1(C)C=CC=CC=1.C(OCC)(=O)C.CC([O-])=O.CC([O-])=O.[Pd+2].O>[CH:31]1([C:2]2[CH:3]=[C:4]3[C:9](=[C:10]([F:12])[CH:11]=2)[C:8](=[O:13])[NH:7][CH2:6][CH2:5]3)[CH2:32][CH2:27]1Participants
9
Reactant 4
Product 1
Reagents, catalysts & solvents 4
Conditions
- Temperature
- 100 °C
Procedure
To a mixture of 6-bromo-8-fluoro-3,4-dihydro-2H-isoquinolin-1-one (1.6 g, 6.5 mmol), tricyclohexylphosphine (0.182 g, 0.65 mmol) and Pd(OAc)2 (0.072 g, 0.032 mmol) in 15 ml toluene placed under argon in a pressure flask was added cyclopropyl boronic acid (1.12 g, 13 mmol), potassium phosphate (6.9 g, 32.5 mmol) and 1.5 ml water. The flask was sealed and the mixture was heated under stirring for 4 hours at 100° C. After cooling the reaction mixture was diluted with ethyl acetate and the organic phase washed with brine, dried with sodium sulfate and concentrated. The residue was purified by flash chromatography (ethyl acetate) affording 0.93 g (71.5% yield) of I.
Workup
- customplaced under argon in a pressure flask
- customThe flask was sealed
- temperaturethe mixture was heated
- temperatureAfter cooling the reaction mixture
- washthe organic phase washed with brine
- dry with materialdried with sodium sulfate
- concentrationconcentrated
- customThe residue was purified by flash chromatography (ethyl acetate)
Sources & evidence
- ORD record
- ord-ba35b7b5d356428ca7a788f395099874
- Source dataset
- uspto-grants-2012_10
- Patent number
- US08299077B2
Reaction notes
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