Sodium Carbonate → 4-Methyl-6-phenylpyrimidine

HRID 2275979Notes

Reaction equation

HRID 2275979 reaction equation
Cl[C:2]1[CH:7]=[C:6]([CH3:8])[N:5]=[CH:4][N:3]=1.[C:9]1(B(O)O)[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=1.C(=O)([O-])[O-].[Na+].[Na+]>C1C=CC(P(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.C1C=CC(P(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.Cl[Pd]Cl.ClCCl.O.C(#N)C>[CH3:8][C:6]1[CH:7]=[C:2]([C:9]2[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=2)[N:3]=[CH:4][N:5]=1

Participants

9

Reactant 3

HCID 10340Sodium Carbonate2×HCID 66827Phenylboronic Acid2×HCID 5817964-Chloro-6-methylpyrimidine

Product 1

HCID 5984294-Methyl-6-phenylpyrimidine

Reagents, catalysts & solvents 5

HCID 6102075Dichlorobis(triphenylphosphine)palladiumCatalystHCID 178418476HCID 178418476, compoundCatalystHCID 962WaterSolvent3×HCID 6342AcetonitrileSolvent2×HCID 6344DichloromethaneSolvent

Procedure

First, 4.90 g of 4-chloro-6-methylpyrimidine, 4.80 g of phenylboronic acid, 4.03 g of sodium carbonate, 0.16 g of bis(triphenylphosphine)palladium(II)dichloride (abbreviation: Pd(PPh3)2Cl2), 20 mL of water, and 10 mL of acetonitrile were put into a recovery flask equipped with a reflux pipe, and the air in the flask was replaced with argon. This reaction container was heated by irradiation with microwaves (2.45 GHz, 100 W) for 60 minutes. Here, there were further put 2.28 g of phenylboronic acid, 2.02 g of sodium carbonate, 0.082 g of Pd(PPh3)2Cl2, 5 mL of water, and 10 mL of acetonitrile into the flask, and the mixture was heated again by irradiation with microwaves (2.45 GHz, 100 W) for 60 minutes. After that, water was added to this solution and extraction with dichloromethane was carried out. The obtained solution of the extract was washed with a saturated sodium carbonate aqueous solution, water, and saturated saline in this order and dried with magnesium sulfate. The solution after drying was filtered. The solvent of this solution was distilled off, and then the obtained residue was purified by silica gel column chromatography using dichloromethane and ethyl acetate as a developing solvent in a volume ratio of 9:1, so that an objective pyrimidine derivative Hmppm (orange oily substance, 46% in yield) was obtained. Note that for the irradiation with microwaves, a microwave synthesis system (Discover, manufactured by CEM Corporation) was used. A synthesis scheme (b-1) of Step 1 is shown below.

Workup

  1. customequipped with a reflux pipe
  2. temperatureThis reaction container was heated by irradiation with microwaves (2.45 GHz, 100 W) for 60 minutes
  3. temperaturethe mixture was heated again by irradiation with microwaves (2.45 GHz, 100 W) for 60 minutes
  4. washThe obtained solution of the extract was washed with a saturated sodium carbonate aqueous solution, water, and saturated saline in this order
  5. dry with materialdried with magnesium sulfate
  6. customThe solution after drying
  7. filtrationwas filtered
  8. distillationThe solvent of this solution was distilled off
  9. customthe obtained residue was purified by silica gel column chromatography

Sources & evidence

ORD record
ord-4d1239cda60f4d199a4c03abc9eb5951
Source dataset
uspto-grants-2015_09
Patent number
US09130184B2

Reaction notes

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