Cesium carbonate → 4-Chloro-5-methyl-6-phenylpyrimidine

HRID 1499033Notes

Reaction equation

HRID 1499033 reaction equation
[Cl:1][C:2]1[C:7]([CH3:8])=[C:6](Cl)[N:5]=[CH:4][N:3]=1.[C:10]1(B(O)O)[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=1.C1(P(C2CCCCC2)C2CCCCC2)CCCCC1.C(=O)([O-])[O-].[Cs+].[Cs+]>C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd].O1CCOCC1>[Cl:1][C:2]1[C:7]([CH3:8])=[C:6]([C:10]2[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=2)[N:5]=[CH:4][N:3]=1

Participants

7

Reactant 4

HCID 10796Cesium carbonateHCID 66827Phenylboronic AcidHCID 75806TricyclohexylphosphineHCID 8188604,6-Dichloro-5-methylpyrimidine

Product 1

HCID 597627694-Chloro-5-methyl-6-phenylpyrimidineYield 37%

Reagents, catalysts & solvents 2

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 312751,4-DioxaneSolvent

Procedure

Into a recovery flask equipped with a reflux pipe, 4.9 g of 4,6-dichloro-5-methylpyrimidine, 3.7 g of phenylboronic acid, 2.3 mL of PCy3, 20 g of cesium carbonate, 0.41 g of Pd2(dba)3, and 40 mL of dioxane were put, and the air in the flask was replaced by argon. This reaction container was heated by irradiation with microwaves (2.45 GHz, 300 W) for 100 minutes. The solvent of this solution was distilled off, and then the obtained residue was purified by flash column chromatography (silica gel) using a mixed solvent of dichloromethane and hexane as a developing solvent in a volume ratio of 7:3, to give 4-chloro-5-methyl-6-phenylpyrimidine (yellow oily substance, 37% in yield). Note that the irradiation with microwaves was performed using a microwave synthesis system (MicroSYNTH, manufactured by Milestone General K.K.). The synthesis scheme of Step 1 is shown by (a-3).

Workup

  1. temperatureThis reaction container was heated by irradiation with microwaves (2.45 GHz, 300 W) for 100 minutes
  2. distillationThe solvent of this solution was distilled off
  3. customthe obtained residue was purified by flash column chromatography (silica gel)

Sources & evidence

ORD record
ord-93bec48ed8544375af8f8fff51b9b672
Source dataset
uspto-grants-2015_12
Patent number
US09200022B2

Reaction notes

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