Dimethylformamide → Methyl 2-phenylpyrimidine-5-carboxylate

HRID 915629Notes

Reaction equation

HRID 915629 reaction equation
[CH3:1][O:2][C:3]([C:5]1[CH:10]=[N:9][C:8](Cl)=[CH:7]N=1)=[O:4].[C:12]1(B(O)O)C=[CH:16][CH:15]=[CH:14][CH:13]=1.[F-].[Cs+].C([O-])([O-])=O.[Na+].[Na+].[CH3:29][N:30](C)C=O>O.C(OCC)(=O)C.CC([O-])=O.CC([O-])=O.[Pd+2]>[CH3:1][O:2][C:3]([C:5]1[CH:10]=[N:9][C:8]([C:7]2[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=2)=[N:30][CH:29]=1)=[O:4]

Participants

9

Reactant 5

HCID 6228DimethylformamideHCID 10340Sodium CarbonateHCID 25953Cesium fluorideHCID 66827Phenylboronic AcidHCID 406081Methyl 5-chloropyrazine-2-carboxylate

Product 1

HCID 11206661Methyl 2-phenylpyrimidine-5-carboxylate

Reagents, catalysts & solvents 3

HCID 167845palladium(II) acetateCatalystHCID 962WaterSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
80 °C

Procedure

Combine 5-chloropyrazine-2-carboxylic acid methyl ester (626 mg, 3.64 mmol), phenylboronic acid (666 mg, 5.45 mmol), cesium fluoride (55 mg, 0.36 mmol) and Na2CO3 (964 mg, 9.09 mmol) in dimethylformamide (5 mL) and water (5 mL) with stirring. Place the hetereogeneous reaction mixture, open to the air, in an oil bath maintained at 80° C. After 5 minutes of heating, add Pd(OAc)2 (81 mg 0.36 mmol) in one portion and stir until reaction turns black. Cool the reaction to room temperature, dilute with ethyl acetate, and filter through a short plug of celite with additional ethyl acetate. Wash the organics with water, dry over magnesium sulfate, filter and evaporate. Purification by flash column chromatography yields 2-phenylpyrimidine-5-carboxylic acid methyl ester as a yellow solid. Dissolve the purified ester in tetrahydrofuran (0.25M) and add an equal volume of 1M sodium hydroxide. Stir vigorously at room temperature for 15 hours. Upon completion, acidify the reaction with conc. HCl and extract with ethyl acetate. Evaporation of the solvent yields 63 mg (8%) of the title compound. 1H NMR (dimethylsulfoxide): 9.37 (s, 1H), 9.21 (s, 1H), 8.23-8.21 (m, 2H), 7.57-7.77 (m, 3H).

Workup

  1. temperatureAfter 5 minutes of heating
  2. temperatureCool
  3. customthe reaction to room temperature
  4. filtrationfilter through a short plug of celite with additional ethyl acetate
  5. washWash the organics with water
  6. dry with materialdry over magnesium sulfate
  7. filtrationfilter
  8. customevaporate
  9. customPurification by flash column chromatography

Sources & evidence

ORD record
ord-2ccd8c9a9fb1472ab6c358263a8bd870
Source dataset
uspto-grants-2007_09
Patent number
US07265246B2

Reaction notes

Loading…