Sodium Carbonate → 4-Chloro-6-(2,5-dimethylphenyl)pyrimidine

HRID 2174173Notes

Reaction equation

HRID 2174173 reaction equation
[Cl:1][C:2]1[CH:7]=[C:6](Cl)[N:5]=[CH:4][N:3]=1.[CH3:9][C:10]1[CH:15]=[CH:14][C:13]([CH3:16])=[CH:12][C:11]=1B(O)O.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>[Cl:1][C:2]1[CH:7]=[C:6]([C:11]2[CH:12]=[C:13]([CH3:16])[CH:14]=[CH:15][C:10]=2[CH3:9])[N:5]=[CH:4][N:3]=1

Participants

8

Reactant 3

HCID 10340Sodium Carbonate2×HCID 709434,6-DichloropyrimidineHCID 2734347(2,5-Dimethylphenyl)boronic acid2×

Product 1

HCID 249022254-Chloro-6-(2,5-dimethylphenyl)pyrimidineYield 64%

Reagents, catalysts & solvents 4

HCID 6102075Dichlorobis(triphenylphosphine)palladiumCatalystHCID 178418476HCID 178418476, compoundCatalystHCID 962WaterSolvent2×HCID 6342AcetonitrileSolvent

Procedure

First, 4.97 g of 4,6-dichloropyrimidine, 5.02 g of 2,5-dimethylphenylboronic acid, 3.55 g of sodium carbonate, 0.29 g of bis(triphenylphosphine)palladium(II)dichloride (abbreviation: Pd(PPh3)2Cl2), 20 mL of water, and 20 mL of acetonitrile were put in a recovery flask equipped with a reflux pipe, and the air in the flask was replaced with argon. This reaction container was heated by being irradiated with microwaves (2.45 GHz, 100 W) for 30 minutes. Further, 1.25 g of 2,5-dimethylphenylboronic acid, 0.89 g of sodium carbonate, and 0.073 g of Pd(PPh3)2Cl2 were put in the flask, and the reaction container was heated again by being irradiated with microwaves (2.45 GHz, 100 W) for 30 minutes. Then, water was added to this solution and an organic layer was extracted with dichloromethane. The obtained organic layer was washed with water and saturated brine, and was 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 flash column chromatography using hexane and ethyl acetate in a ratio of 5:1 as a developing solvent, so that the target pyrimidine derivative was obtained (pale yellow oily substance, yield of 64%). A synthetic scheme of Step 1 is shown in (d−1) below.

Workup

  1. customequipped with a reflux pipe
  2. temperatureThis reaction container was heated
  3. customby being irradiated with microwaves (2.45 GHz, 100 W) for 30 minutes
  4. temperaturethe reaction container was heated again
  5. customby being irradiated with microwaves (2.45 GHz, 100 W) for 30 minutes
  6. extractionan organic layer was extracted with dichloromethane
  7. washThe obtained organic layer was washed with water and saturated brine
  8. dry with materialwas dried with magnesium sulfate
  9. filtrationAfter the drying, the solution was filtered
  10. distillationThe solvent of this solution was distilled off
  11. customthe obtained residue was purified by flash column chromatography

Sources & evidence

ORD record
ord-addeae44c9f84df282faff19d92e62a5
Source dataset
uspto-grants-2015_06
Patent number
US09059414B2

Reaction notes

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