Sodium Carbonate → 4-Methyl-6-phenylpyrimidine

HRID 2177471Notes

Reaction equation

HRID 2177471 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.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 6102075Dichlorobis(triphenylphosphine)palladiumCatalystHCID 178418476HCID 178418476, compoundCatalystHCID 962WaterSolvent3×HCID 6342AcetonitrileSolvent2×

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 60 minutes so that heating was performed. 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 subjected to irradiation with microwaves (2.45 GHz, 100 W) for 60 minutes so that heating was performed. After that, water was added to this solution and an organic layer was subjected to extraction with dichloromethane. The solution of the obtained extract was washed with a saturated sodium carbonate aqueous solution, water, and saturated brine in this order and dried over 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. As a result, a pyrimidine derivative Hmppm, which was the object of the synthesis, was obtained (orange oily substance, 46% yield). Note that for the microwave irradiation, a microwave synthesis system (Discover, produced by CEM Corporation) was used. A synthesis scheme (y-1) of Step 1 is illustrated 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 60 minutes so
  3. temperaturethat heating
  4. customthe mixture was subjected to irradiation with microwaves (2.45 GHz, 100 W) for 60 minutes so
  5. temperaturethat heating
  6. extractionan organic layer was subjected to extraction with dichloromethane
  7. extractionThe solution of the obtained extract
  8. washwas washed with a saturated sodium carbonate aqueous solution, water, and saturated brine in this order
  9. dry with materialdried over magnesium sulfate
  10. filtrationAfter the drying, the solution was filtered
  11. distillationThe solvent of this solution was distilled off
  12. customthe obtained residue was purified by silica gel column chromatography
  13. customthe object of the synthesis
  14. customwas obtained (orange oily substance, 46% yield)
  15. customNote that for the microwave irradiation
  16. customa microwave synthesis system (Discover, produced by CEM Corporation)
  17. customA synthesis scheme (y-1) of Step 1

Sources & evidence

ORD record
ord-9addf91fe2d5416faf3873bafbb8528f
Source dataset
uspto-grants-2015_06
Patent number
US09067916B2

Reaction notes

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