Sodium Carbonate → 4-chloro-5-methyl-6-[4-(trifluoromethyl)phenyl]Pyrimidine

HRID 1269643Notes

Reaction equation

HRID 1269643 reaction equation
[Cl:1][C:2]1[C:7]([CH3:8])=[C:6](Cl)[N:5]=[CH:4][N:3]=1.C(=O)([O-])[O-].[Na+].[Na+].[F:16][C:17]([F:28])([F:27])[C:18]1[CH:23]=[CH:22][C:21](B(O)O)=[CH:20][CH:19]=1>C(COC)OC.O.C(Cl)(Cl)Cl.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>[Cl:1][C:2]1[C:7]([CH3:8])=[C:6]([C:21]2[CH:22]=[CH:23][C:18]([C:17]([F:28])([F:27])[F:16])=[CH:19][CH:20]=2)[N:5]=[CH:4][N:3]=1

Participants

8

Reactant 3

HCID 10340Sodium CarbonateHCID 8188604,6-Dichloro-5-methylpyrimidineHCID 27343894-(Trifluoromethyl)phenylboronic acid

Product 1

HCID 184484034-chloro-5-methyl-6-[4-(trifluoromethyl)phenyl]PyrimidineYield 65.8%

Reagents, catalysts & solvents 4

HCID 178418397HCID 178418397, compoundCatalystHCID 962WaterSolvent2×HCID 6212ChloroformSolventHCID 80711,2-DimethoxyethaneSolvent

Procedure

To a solution of 4,6-dichloro-5-methylpyrimidine (1 g, 6.13 mmol) in dimethoxyethane (28 mL) and water (14 mL) was added sodium carbonate (1.69 g, 16.0 mmol), 4-trifluoromethylphenylboronic acid (1.165 g, 6.13 mmol) and tetrakis(triphenylphosphine)palladium (0) (0.14 g). The resulting mixture was heated at reflux under nitrogen for 18 h, the reaction mixture was allowed to cool to room temperature and diluted with water (100 mL) before extraction into CHCl3 (2×100 mL). The organic solution separated by hydrophobic frit and the solvents removed in vacuo. Purification by Biotage™ chromatography (Silica, 90 g) eluting with 19:1 cyclohexane:EtOAc afforded the title compound as a white solid (1.1 g).

Workup

  1. temperatureThe resulting mixture was heated
  2. temperatureat reflux under nitrogen for 18 h
  3. customThe organic solution separated by hydrophobic frit
  4. customthe solvents removed in vacuo
  5. customPurification by Biotage™ chromatography (Silica, 90 g)
  6. washeluting with 19:1 cyclohexane

Sources & evidence

ORD record
ord-2822fa15dee146058f726a75e6d8a227
Source dataset
uspto-grants-2007_04
Patent number
US07199239B2

Reaction notes

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