Potassium Carbonate → 4-(4-(Trifluoromethyl)phenyl)pyrimidin-2(1H)-one

HRID 474937Notes

Reaction equation

HRID 474937 reaction equation
Cl[C:2]1[CH:7]=[CH:6][N:5]=[C:4]([O:8]C)[N:3]=1.[F:10][C:11]([F:22])([F:21])[C:12]1[CH:17]=[CH:16][C:15](B(O)O)=[CH:14][CH:13]=1.C([O-])([O-])=O.[K+].[K+].C([O-])(O)=O.[Na+]>CS(C)=O.Cl.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]>[F:10][C:11]([F:22])([F:21])[C:12]1[CH:17]=[CH:16][C:15]([C:2]2[CH:7]=[CH:6][NH:5][C:4](=[O:8])[N:3]=2)=[CH:14][CH:13]=1

Participants

8

Reactant 4

HCID 11430Potassium CarbonateHCID 516892Sodium BicarbonateHCID 5752304-Chloro-2-methoxypyrimidineHCID 27343894-(Trifluoromethyl)phenylboronic acid

Product 1

HCID 1785174734-(4-(Trifluoromethyl)phenyl)pyrimidin-2(1H)-oneYield 22.2%

Reagents, catalysts & solvents 3

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)CatalystHCID 313Hydrochloric AcidSolventHCID 679Dimethyl SulfoxideSolvent

Conditions

Temperature
95 °C

Procedure

A suspension of 4-chloro-2-methoxypyrimidine (500 mg, 3.47 mmol), 4-(trifluoromethyl)phenylboronic acid (788 mg, 4.17 mmol), PdCl2(dppf) (283 mg, 0.347 mmol) and K2CO3 (958 mg, 6.94 mmol) in DMSO (10 mL) was degassed under reduced pressure for 45 min. The suspension was put under N2 and stirred at 95° C. for 20 h. The suspension was cooled, H2O was added and the suspension was filtered to afford a light colored solid. Flash chromatography on silica gel (hexanes/(1:1 EtOAc/hexanes), 100:0 to 0:100) afforded a white solid. The white solid was diluted with concentrated HCl solution (10 mL) and stirred at reflux for 4 h. The reaction was cooled, and the solution was neutralized with saturated NaHCO3 solution. The resulting suspension was filtered to afford 185 mg (22%) of the title compound as a white solid: ESI MS m/z 241 [M+H]+.

Workup

  1. customwas degassed under reduced pressure for 45 min
  2. temperatureThe suspension was cooled
  3. additionH2O was added
  4. filtrationthe suspension was filtered
  5. customto afford a light colored solid
  6. customFlash chromatography on silica gel (hexanes/(1:1 EtOAc/hexanes), 100:0 to 0:100) afforded a white solid
  7. stirringstirred
  8. temperatureat reflux for 4 h
  9. temperatureThe reaction was cooled
  10. filtrationThe resulting suspension was filtered

Sources & evidence

ORD record
ord-5b9fd642f48d4660821fe3e7aae7944a
Source dataset
uspto-grants-2014_01
Patent number
US08637501B2

Reaction notes

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