Potassium Phosphate, Tribasic → 2-chloro-4-cyclopropyl-5-fluoroPyrimidine
Reaction equation
[F:1][C:2]1[C:3](Cl)=[N:4][C:5]([Cl:8])=[N:6][CH:7]=1.[CH:10]1(B(O)O)[CH2:12][CH2:11]1.[O-]P([O-])([O-])=O.[K+].[K+].[K+]>C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2].ClCCl>[Cl:8][C:5]1[N:4]=[C:3]([CH:10]2[CH2:12][CH2:11]2)[C:2]([F:1])=[CH:7][N:6]=1Participants
Conditions
- Temperature
- 67 °C
Procedure
5-Fluoro-2,4-dichloropyrimidine (5 g, 29.9 mmol), cyclopropyl boronic acid (2.57 g, 29.9 mmol), potassium phosphate tribasic (15.89 g, 74.9 mmol) and PdCl2(dppf)-dichloromethane adduct (1.223 g, 1.497 mmol) were added to a dry flask. The system was degassed with argon, and then tetrahydrofuran (150 mL) was added. The reaction mixture was degassed with argon for five minutes, and then heated to 67° C. After 12 hours, the reaction mixture was diluted with ethyl acetate (1000 mL), washed with brine, dried over magnesium sulfate, filtered and concentrated. The residue was purified by column chromatography on silica gel, eluting with ethyl acetate in hexanes to afford 2-chloro-4-cyclopropyl-5-fluoropyrimidine (4.1 g, 23.8 mmol, 79% yield). MS ESI: [M+H]+ m/z 172.9.
Workup
- customThe system was degassed with argon
- additiontetrahydrofuran (150 mL) was added
- customThe reaction mixture was degassed with argon for five minutes
- additionthe reaction mixture was diluted with ethyl acetate (1000 mL)
- washwashed with brine
- dry with materialdried over magnesium sulfate
- filtrationfiltered
- concentrationconcentrated
- customThe residue was purified by column chromatography on silica gel
- washeluting with ethyl acetate in hexanes
Sources & evidence
- ORD record
- ord-95825331fc5a4026816623ca5d727f97
- Source dataset
- uspto-grants-2013_10
- Patent number
- US08551984B2
Reaction notes
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