Dimethylformamide → Methyl 2-phenylpyrimidine-5-carboxylate

HRID 2224719Notes

Reaction equation

HRID 2224719 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=O)C>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 DMF (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 MgSO4, 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 THF (0.25M) and add an equal volume of 1M NaOH. 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 (DMSO): 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 MgSO4
  7. filtrationfilter
  8. customevaporate
  9. customPurification by flash column chromatography

Sources & evidence

ORD record
ord-11e23d47d69646a996537c6168f7b0bf
Source dataset
uspto-grants-2008_05
Patent number
US07378447B2

Reaction notes

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