1,2-Dimethoxyethane → 2-Chloro-4-(4-(trifluoromethyl)phenyl)pyrimidine
Reaction equation
[Cl:1][C:2]1[N:7]=[C:6](Cl)[CH:5]=[CH:4][N:3]=1.[F:9][C:10]([F:21])([F:20])[C:11]1[CH:16]=[CH:15][C:14](B(O)O)=[CH:13][CH:12]=1.P([O-])([O-])([O-])=O.[K+].[K+].[K+].COCCOC>C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.O>[Cl:1][C:2]1[N:7]=[C:6]([C:14]2[CH:15]=[CH:16][C:11]([C:10]([F:21])([F:20])[F:9])=[CH:12][CH:13]=2)[CH:5]=[CH:4][N:3]=1Participants
Reactant 4
Product 1
Reagents, catalysts & solvents 2
Conditions
- Temperature
- 80 °C
Procedure
A mixture of 2,4-dichloro-pyrimidine (4.0 g, 27 mmol), 4-trifluoromethyl phenyl boronic acid (5.1 g, 27 mmol), tetrakis(triphenylphosphine)palladium(0) (1.5 g, 1.3 mmol), potassium phosphate (11 g, 54 mmol), 1,2-dimethoxyethane (50 mL) and water (10 mL) was heated to 80° C. under a blanket of nitrogen in a sealed tube. After 5 h, the mixture was partitioned between water (50 mL) and ethyl acetate (50 mL). The aqueous layer was extracted with ethyl acetate (3×50 mL). The combined organic layers were dried (MgSO4), filtered, and concentrated. The residue was purified directly by FCC to afford a white solid (5.0 g, 72%). MS (ESI): mass calcd. for C11H6ClF3N2, 258.0; m/z found, 259.0 [M+H]+. 1H NMR (500 MHz, CDCl3) δ 8.74 (d, J=5.2, 1H), 8.23 (d, J=8.1, 2H), 7.80 (d, J=8.2, 2H), 7.71 (d, J=5.2, 1H).
Workup
- customthe mixture was partitioned between water (50 mL) and ethyl acetate (50 mL)
- extractionThe aqueous layer was extracted with ethyl acetate (3×50 mL)
- dry with materialThe combined organic layers were dried (MgSO4)
- filtrationfiltered
- concentrationconcentrated
- customThe residue was purified directly by FCC
Sources & evidence
- ORD record
- ord-60588fd86e34447fb95f5c114d27a6b9
- Source dataset
- uspto-grants-2013_12
- Patent number
- US08614201B2
Reaction notes
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