Sodium Carbonate → 1,1-Dimethylethyl 3-(5-cyano-1-isoquinolinyl)propanoate

HRID 2192491Notes

Reaction equation

Br[C:2]1[CH:11]=[CH:10][CH:9]=[C:8]2[C:3]=1[CH:4]=[CH:5][N:6]=[C:7]2[CH2:12][CH2:13][C:14]([O:16][C:17]([CH3:20])([CH3:19])[CH3:18])=[O:15].C(=O)([O-])[O-].[Na+].[Na+].C[C:28]([N:30](C)C)=O>C(OCC)(=O)C.C([O-])(=O)C.[Pd+2].C([O-])(=O)C>[C:28]([C:2]1[CH:11]=[CH:10][CH:9]=[C:8]2[C:3]=1[CH:4]=[CH:5][N:6]=[C:7]2[CH2:12][CH2:13][C:14]([O:16][C:17]([CH3:20])([CH3:19])[CH3:18])=[O:15])#[N:30]

Participants

Conditions

Temperature: 120 °C

Procedure

1,1-Dimethylethyl 3-(5-bromo-1-isoquinolinyl)propanoate (D34; 60 g, 178 mmol) was taken up in dry DMA (600 ml) followed by the addition of potassium hexacyanoferrate hexahydrate (22.61 g, 53.5 mmol) then palladium acetate (0.801 g, 3.57 mmol) dppf (3.96 g, 7.14 mmol) and then finally sodium carbonate (22.7 g, 214 mmol). The reaction mixture was stirred at 120° C. overnight, cooled and diluted with ethyl acetate (500 ml) and filtered through Celite. The filtrate was concentrated in vacuo. and the dark residue was taken up in DCM (250 ml) and filtered through Celite and cotton wool. The DCM solution (250 ml) was purified by chromatography using a gradient system 0-100% ethyl acetate in isohexane to give the title compound (25.3 g)

Workup

temperaturecooled
filtrationfiltered through Celite
concentrationThe filtrate was concentrated in vacuo
filtrationfiltered through Celite and cotton wool
customThe DCM solution (250 ml) was purified by chromatography

Sources & evidence

ORD record: ord-60902b9976b64e0da0c5507f0d5ae86e
Source dataset: uspto-grants-2012_12
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08329730B2

Reaction notes

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