Sodium Carbonate → 4-(6-(Trifluoromethyl)pyridin-3-yl)phenol

HRID 1619671Notes

Reaction equation

Br[C:2]1[CH:3]=[CH:4][C:5]([C:8]([F:11])([F:10])[F:9])=[N:6][CH:7]=1.[OH:12][C:13]1[CH:18]=[CH:17][C:16](B(O)O)=[CH:15][CH:14]=1.C(=O)([O-])[O-].[Na+].[Na+]>O1CCOCC1.O.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd]>[F:9][C:8]([F:11])([F:10])[C:5]1[N:6]=[CH:7][C:2]([C:16]2[CH:17]=[CH:18][C:13]([OH:12])=[CH:14][CH:15]=2)=[CH:3][CH:4]=1

Participants

Conditions

Temperature: 70 °C

Procedure

5-Bromo-2-(trifluoromethyl)pyridine (1.18 g, 5.51 mmol), 4-hydroxyphenylboronic acid (775 mg, 5.51 mmol) and sodium carbonate (2.34 g, 22.0 mmol) were combined and dissolved in a mixture of dioxane/water (30 mL/6 mL). The reaction mixture was degassed and then tetrakistriphenylphosphinepalladium (0) (322 mg, 0.275 mmol) was added and the reaction mixture was heated at 70° C. for 18 hours. The cooled reaction mixture was partitioned between ethyl acetate and water. The organic layer was separated and washed with brine, dried over anhydrous MgSO4 and concentrated in vacuo. The residue was purified on silica gel by Biotage™ (7% to 60% EtOAc in heptane over 20 CV) to give the title compound (1.24 g, 95%) as a white solid.

Workup

customThe reaction mixture was degassed
customThe cooled reaction mixture
customwas partitioned between ethyl acetate and water
customThe organic layer was separated
washwashed with brine
dry with materialdried over anhydrous MgSO4
concentrationconcentrated in vacuo
customThe residue was purified on silica gel by Biotage™ (7% to 60% EtOAc in heptane over 20 CV)

Sources & evidence

ORD record: ord-cae567cf9a6d49b5be1b557c16adf041
Source dataset: uspto-grants-2014_07
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08772293B2

Reaction notes

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