Sodium Carbonate → 4-Methyl-6-phenylpyrimidine

HRID 1629576Notes

Reaction equation

HRID 1629576 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+]>Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1.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

8

Reactant 3

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

Product 1

HCID 5984294-Methyl-6-phenylpyrimidineYield 46%

Reagents, catalysts & solvents 4

HCID 178418476HCID 178418476, compoundCatalyst2×HCID 962WaterSolvent3×HCID 6342AcetonitrileSolvent2×HCID 6344DichloromethaneSolvent

Procedure

First, in a recovery flask equipped with a reflux pipe were put 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, 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, in the flask 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, 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. After the drying, the solution 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 a pyrimidine derivative Hmppm, which was the objective substance, was obtained (orange oily substance, yield of 46%). Note that the irradiation with microwaves was performed using a microwave synthesis system (Discover, manufactured by CEM Corporation). The synthesis scheme of Step 1 is shown in (b-1) below.

Workup

  1. customFirst, in a recovery flask equipped 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. filtrationAfter the drying, the solution was filtered
  7. distillationThe solvent of this solution was distilled off
  8. customthe obtained residue was purified by silica gel column chromatography
  9. customwas obtained (orange oily substance, yield of 46%)
  10. customNote that the irradiation with microwaves
  11. customa microwave synthesis system (Discover, manufactured by CEM Corporation)
  12. customThe synthesis scheme of Step 1

Sources & evidence

ORD record
ord-13e7dfbaf84b4fbeb6ca90ab12fc7f8e
Source dataset
uspto-grants-2014_07
Patent number
US08789968B2

Reaction notes

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