Sodium Carbonate → 2-(2,6-Dimethylphenyl)-5-[(5-isopropyl-2-methylphenoxy)methyl]-4-methoxy-6-methylpyrimidine

HRID 1455771

Reaction equation

HRID 1455771 reaction equation
Cl[C:2]1[N:7]=[C:6]([O:8][CH3:9])[C:5]([CH2:10][O:11][C:12]2[CH:17]=[C:16]([CH:18]([CH3:20])[CH3:19])[CH:15]=[CH:14][C:13]=2[CH3:21])=[C:4]([CH3:22])[N:3]=1.[CH3:23][C:24]1[CH:29]=[CH:28][CH:27]=[C:26]([CH3:30])[C:25]=1B(O)O.C(=O)([O-])[O-].[Na+].[Na+]>O1CCOCC1>[CH3:23][C:24]1[CH:29]=[CH:28][CH:27]=[C:26]([CH3:30])[C:25]=1[C:2]1[N:7]=[C:6]([O:8][CH3:9])[C:5]([CH2:10][O:11][C:12]2[CH:17]=[C:16]([CH:18]([CH3:20])[CH3:19])[CH:15]=[CH:14][C:13]=2[CH3:21])=[C:4]([CH3:22])[N:3]=1

Participants

5

Reactant 3

HCID 10340Sodium CarbonateHCID 5833222,6-Dimethylphenylboronic acidHCID 575314062-Chloro-5-[(5-isopropyl-2-methylphenoxy)methyl]-4-methoxy-6-methylpyrimidine

Product 1

HCID 575314972-(2,6-Dimethylphenyl)-5-[(5-isopropyl-2-methylphenoxy)methyl]-4-methoxy-6-methylpyrimidine

Reagents, catalysts & solvents 1

HCID 312751,4-DioxaneSolvent

Conditions

Temperature
90 °C

Procedure

A mixture containing 2-chloro-5-[(5-isopropyl-2-methylphenoxy)methyl]-4-methoxy-6-methylpyrimidine (˜3.91 mmol), 2,6-dimethylphenylboronic acid (1.17 g, 7.82 mmol), 15.6 mL of 1 M aqueous sodium carbonate and dioxane (56 mL) is degassed by bubbling with argon for 20 min. To this mixture is added Pd(PPh3)4 (226 mg, 0.05 mol %). The resulting yellow mixture is heated at 90° C. under nitrogen with magnetic stirring for 24 h. Another 50 mg of Pd(PPh3)4 is added and heating is continued for another 18 h until the reaction is complete by LC/MS analysis. The reaction mixture is allowed to cool to ambient temperature and partitioned between EtOAc (200 mL) and water (70 mL). The organic layer is separated, extracted with water (70 mL×2), brine (70 mL), dried over anhydrous sodium sulfate, filtered and evaporated to obtain a yellow oil. Purification by chromatography on silica gel (5-50% EtOAc/Hexanes) provides the title compound as a colorless solid. LC-MS found 391.4 (MH+), rt=1.93 min.

Workup

  1. customis degassed
  2. customby bubbling with argon for 20 min
  3. additionTo this mixture is added Pd(PPh3)4 (226 mg, 0.05 mol %)
  4. additionAnother 50 mg of Pd(PPh3)4 is added
  5. temperatureheating
  6. waitis continued for another 18 h until the reaction
  7. temperatureto cool to ambient temperature
  8. custompartitioned between EtOAc (200 mL) and water (70 mL)
  9. customThe organic layer is separated
  10. extractionextracted with water (70 mL×2), brine (70 mL)
  11. dry with materialdried over anhydrous sodium sulfate
  12. filtrationfiltered
  13. customevaporated
  14. customto obtain a yellow oil
  15. customPurification by chromatography on silica gel (5-50% EtOAc/Hexanes)

Sources & evidence

ORD record
ord-fbd59768edac4db488a55f802e553032
Source dataset
uspto-grants-2009_01
Patent number
US07482350B2

Linked notes

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