Sodium Bicarbonate → 2-(4-(Trifluoromethoxy)phenyl)isonicotinonitrile

HRID 1479806Notes

Reaction equation

Cl[C:2]1[CH:7]=[C:6]([C:8]#[N:9])[CH:5]=[CH:4][N:3]=1.[F:10][C:11]([F:23])([F:22])[O:12][C:13]1[CH:18]=[CH:17][C:16](B(O)O)=[CH:15][CH:14]=1.C([O-])(O)=O.[Na+]>COCCOC.O>[F:10][C:11]([F:22])([F:23])[O:12][C:13]1[CH:18]=[CH:17][C:16]([C:2]2[CH:7]=[C:6]([C:8]#[N:9])[CH:5]=[CH:4][N:3]=2)=[CH:15][CH:14]=1

Participants

Conditions

Temperature: 100 °C

Procedure

A solution of 19 (2.5 g, 18 mmol) in DME (90 mL) was added 4-trifluoromethoxy phenyl boronic acid (1.1 mol eq, 4.46 g) and NaHCO3 (3 mol eq, 4.66 g) suspended in water (50 mL). The mixture was degassed under vacuum, then Tetrakispalladium was added (catalytic amount) and the reaction stirred at 100° C. under inert atmosphere for 12 h. The solvent was removed under reduced pressure and water was added to the residue (100 mL). The aqueous phase was extracted with EtOAc (3×50 mL) and the combined organic layer was washed with brine (100 mL) and dried over Na2SO4. The solvent was evaporated under vacuum to obtain 20B as a pale yellow crystals (96% Yield, 4.6 g, 17.4 mmol). 1HNMR (DMSO, 200 MHz) δ 7.5 (dd, 2H, J=2), 7.84 (dd, 1H, J=1.8), 8.31 (d, 2H, J=9.8), 8.54 (d, 1H, J=2), 8.93 (dd, 1H, J=1.9).

Workup

customThe mixture was degassed under vacuum
additionTetrakispalladium was added (catalytic amount)
customThe solvent was removed under reduced pressure and water
additionwas added to the residue (100 mL)
extractionThe aqueous phase was extracted with EtOAc (3×50 mL)
washthe combined organic layer was washed with brine (100 mL)
dry with materialdried over Na2SO4
customThe solvent was evaporated under vacuum

Sources & evidence

ORD record: ord-53dc4cb9b53244d38f989cfc297dbf71
Source dataset: uspto-grants-2016_08
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09409864B2

Reaction notes

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