Sodium Carbonate → 4-Methyl-6-phenylpyrimidine

HRID 1748933Notes

Reaction equation

HRID 1748933 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 subjected to irradiation with microwaves (2.45 GHz, 100 W) for one hour to be heated. 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 then with saturated saline, and dried with magnesium sulfate. The solution which had been dried 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 target 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). A synthesis scheme (b-1) of Step 1 is shown below.

Workup

  1. customFirst, in a recovery flask equipped with a reflux pipe
  2. customThis reaction container was subjected to irradiation with microwaves (2.45 GHz, 100 W) for one hour
  3. temperatureto be heated
  4. temperaturethe mixture was heated again by irradiation with microwaves (2.45 GHz, 100 W) for 60 minutes
  5. washThe obtained solution of the extract was washed with a saturated sodium carbonate aqueous solution, water
  6. dry with materialwith saturated saline, and dried with magnesium sulfate
  7. customThe solution which had been dried
  8. filtrationwas filtered
  9. distillationThe solvent of this solution was distilled off
  10. customthe obtained residue was purified by silica gel column chromatography
  11. customwas obtained (orange oily substance, yield of 46%)
  12. customNote that the irradiation with microwaves
  13. customa microwave synthesis system (Discover, manufactured by CEM Corporation)
  14. customA synthesis scheme (b-1) of Step 1

Sources & evidence

ORD record
ord-a3e1e2ca85374572b629d8045d18494c
Source dataset
uspto-grants-2015_10
Patent number
US09153627B2

Reaction notes

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