Sodium Carbonate → 4-Methyl-6-phenylpyrimidine

HRID 2277574Notes

Reaction equation

HRID 2277574 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-phenylpyrimidineYield 46%

Reagents, catalysts & solvents 5

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

Procedure

Into a recovery flask equipped with a reflux pipe, 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, 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, into the flask, 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 were further put, and the reaction container was heated again by irradiation with microwaves (2.45 GHz, 100 W) for one hour. 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 aqueous solution of sodium carbonate, water, and then with saturated saline, dried with magnesium sulfate, and filtered. The solvent of the filtrate 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, produced by CEM Corporation). A synthesis scheme (b-1) of Step 1 is shown below.

Workup

  1. customThis reaction container was subjected to irradiation with microwaves (2.45 GHz, 100 W) for one hour
  2. temperatureto be heated
  3. temperaturethe reaction container was heated again by irradiation with microwaves (2.45 GHz, 100 W) for one hour
  4. washThe obtained solution of the extract was washed with a saturated aqueous solution of sodium carbonate, water
  5. dry with materialwith saturated saline, dried with magnesium sulfate
  6. filtrationfiltered
  7. distillationThe solvent of the filtrate 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, produced by CEM Corporation)
  12. customA synthesis scheme (b-1) of Step 1

Sources & evidence

ORD record
ord-2218ffc1035c44149f4a8f24ab43043c
Source dataset
uspto-grants-2015_09
Patent number
US09133169B2

Reaction notes

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