Sodium Carbonate → 4-Methyl-6-phenylpyrimidine

HRID 1752164Notes

Reaction equation

HRID 1752164 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

First, 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), 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, 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 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 illustrated 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, and dried with magnesium sulfate
  6. customThe solution which had been dried
  7. filtrationwas filtered
  8. distillationThe solvent of this solution was distilled off
  9. customthe obtained residue was purified by silica gel column chromatography
  10. customwas obtained (orange oily substance, yield of 46%)
  11. customNote that the irradiation with microwaves
  12. customa microwave synthesis system (Discover, produced by CEM Corporation)
  13. customA synthesis scheme (b-1) of Step 1

Sources & evidence

ORD record
ord-ee8cd722573b4b949e77db30b1bfbe91
Source dataset
uspto-grants-2015_10
Patent number
US09162990B2

Reaction notes

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