Sodium Carbonate → 4-Chloro-6-(4-(trifluoromethyl)phenyl)pyrimidine

HRID 747117Notes

Reaction equation

HRID 747117 reaction equation
[Cl:1][C:2]1[CH:7]=[C:6](Cl)[N: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.C(=O)([O-])[O-].[Na+].[Na+]>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.C(#N)C>[Cl:1][C:2]1[CH: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)[N:5]=[CH:4][N:3]=1

Participants

6

Reactant 3

HCID 10340Sodium CarbonateHCID 709434,6-DichloropyrimidineHCID 27343894-(Trifluoromethyl)phenylboronic acid

Product 1

HCID 167478374-Chloro-6-(4-(trifluoromethyl)phenyl)pyrimidine

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 6342AcetonitrileSolvent

Conditions

Temperature
80 °C

Procedure

To a 500-mL, round-bottomed flask was added 4,6-dichloropyrimidine (14 g, 95 mmol, Aldrich), 4-(trifluoromethyl)phenylboronic acid (6.0 g, 32 mmol, Aldrich), acetonitrile (95 mL) and 1 M aq sodium carbonate (95 mL). The mixture was deoxygenated by sparging with N2 for 15 min. The catalyst, Pd(PPh3)4 (1.9 g, 1.6 mmol, Strem), was added and the yellow mixture was heated at 80° C. for 15 h. After cooling to 25° C., the solution was concentrated to remove the acetonitrile. The solution was diluted with aq NaHCO3 and extracted with CH2Cl2. The combined extracts were dried over Na2SO4, filtered and concentrated in vacuo. Purification by silica gel chromatography with gradient from 1.5% to 10% solution of ethyl acetate in hexane afforded the title compound as a white solid. MS (ESI, pos. ion) m/z: 259 (M+1).

Workup

  1. customThe mixture was deoxygenated
  2. customby sparging with N2 for 15 min
  3. temperatureAfter cooling to 25° C.
  4. concentrationthe solution was concentrated
  5. customto remove the acetonitrile
  6. additionThe solution was diluted with aq NaHCO3
  7. extractionextracted with CH2Cl2
  8. dry with materialThe combined extracts were dried over Na2SO4
  9. filtrationfiltered
  10. concentrationconcentrated in vacuo
  11. customPurification by silica gel chromatography with gradient from 1.5% to 10% solution of ethyl acetate in hexane

Sources & evidence

ORD record
ord-dd6a79ec55b342f4bc19d65805842dd2
Source dataset
uspto-grants-2008_07
Patent number
US07396831B2

Reaction notes

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