Cesium carbonate → 4-Pyridinecarbonitrile, 2-methoxy-6-[4-(trifluoromethyl)phenyl]-

HRID 1479868Notes

Reaction equation

Cl[C:2]1[CH:7]=[C:6]([C:8]#[N:9])[CH:5]=[C:4]([O:10][CH3:11])[N:3]=1.[F:12][C:13]([F:24])([F:23])[C:14]1[CH:19]=[CH:18][C:17](B(O)O)=[CH:16][CH:15]=1.C(=O)([O-])[O-].[Cs+].[Cs+].CC(C1C=C(C(C)C)C(C2C=CC=CC=2P(C2CCCCC2)C2CCCCC2)=C(C(C)C)C=1)C>C([O-])(=O)C.[Pd+2].C([O-])(=O)C.O1CCOCC1>[CH3:11][O:10][C:4]1[CH:5]=[C:6]([C:8]#[N:9])[CH:7]=[C:2]([C:17]2[CH:18]=[CH:19][C:14]([C:13]([F:24])([F:23])[F:12])=[CH:15][CH:16]=2)[N:3]=1

Participants

Conditions

Temperature: 100 °C

Procedure

The nitrile 25F (2.3 g, 13.8 mmol), 4-trifluoromethylphenylboronic acid (2.61 g, 1.1 mol eq), palladium acetate (62 mg, 0.02 mol eq), cesium carbonate (8.97 g, 2 mol eq), and XPhos (260 mg, 0.04 mol eq) were mixed, placed under a nitrogen atmosphere and dioxane (10 mL) was added. The mixture was heated at 100° C. for 4 h. After cooling, the mixture was filtered through a celite pad, washed with dioxane (2×30 mL) and concentrated under reduced pressure. The residue was purified by flash chromatography (9:1 petroleum ether:EtOAc) to afford 26I as a pale yellow solid (840 mg, 25% Yield). 1HNMR (DMSO, 200 MHz) δ 4.03 (s, 3H), 7.46 (s, 1H), 7.90 (d, 2H, J=7.8), 8.17 (s, 1H), 8.40 (d, 2H, J=8).

Workup

temperatureAfter cooling
filtrationthe mixture was filtered through a celite pad
washwashed with dioxane (2×30 mL)
concentrationconcentrated under reduced pressure
customThe residue was purified by flash chromatography (9:1 petroleum ether:EtOAc)

Sources & evidence

ORD record: ord-b880c3d143954ca4a4cedc21f787d983
Source dataset: uspto-grants-2016_08
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09409864B2

Reaction notes

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