Reaction equation
[F:1][C:2]([F:13])([F:12])[C:3]1[CH:8]=[CH:7][C:6](B(O)O)=[CH:5][CH:4]=1.COC1C=CC=C(OC)C=1C1C=CC=CC=1P(C1CCCCC1)C1CCCCC1.C(=O)([O-])[O-].[K+].[K+].I[C:50]1[C:55]([O:56][CH3:57])=[CH:54][CH:53]=[C:52]([CH3:58])[N:51]=1>C(#N)C.CC([O-])=O.CC([O-])=O.[Pd+2].O>[CH3:57][O:56][C:55]1[C:50]([C:6]2[CH:7]=[CH:8][C:3]([C:2]([F:13])([F:12])[F:1])=[CH:4][CH:5]=2)=[N:51][C:52]([CH3:58])=[CH:53][CH:54]=1Participants
Reactant 4
Product 1
Reagents, catalysts & solvents 3
Conditions
- Temperature
- 75 °C
Procedure
To a mixture of 4-(trifluoromethyl)phenylboronic acid (0.97 g, 5.1 mmol), S—PHOS (0.20 g, 0.47 mmol), potassium carbonate (2.0 g, 15 mmol), and Pd(OAc)2 (0.061 g, 0.27 mmol) was added a solution of 2-iodo-3-methoxy-6-methylpyridine (prepared in the previous step) in acetonitrile (6 mL) followed by water (4 mL). The reaction mixture was degassed by bubbling nitrogen through the solution for 10 min, and the reaction mixture was heated to 75° C. After 4 h, the reaction mixture was diluted with EtOAc, washed with saturated NaHCO3 (1×), brine (1×), dried over MgSO4, filtered, and concentrated. Purification by flash column chromatography on silica gel (5% to 20% EtOAc in hexanes) gave 3-methoxy-6-methyl-2-(4-(trifluoromethyl)phenyl)pyridine.
Workup
- customThe reaction mixture was degassed
- customby bubbling nitrogen through the solution for 10 min
- additionthe reaction mixture was diluted with EtOAc
- washwashed with saturated NaHCO3 (1×), brine (1×)
- dry with materialdried over MgSO4
- filtrationfiltered
- concentrationconcentrated
- customPurification by flash column chromatography on silica gel (5% to 20% EtOAc in hexanes)
Sources & evidence
- ORD record
- ord-0efef0adc9b44a178b643bef49bc58a1
- Source dataset
- uspto-grants-2014_07
- Patent number
- US08791147B2
Linked notes
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