Potassium Phosphate, Tribasic → 2-[2-(4-Chloro-phenyl)-5-methyl-pyrimidin-4-yl]-cyclopentane-1,3-dione

HRID 2170803Notes

Reaction equation

HRID 2170803 reaction equation
[CH2:1]1[C:6](=[O:7])[CH2:5][C:3](=[O:4])[CH2:2]1.Cl[CH:9]1[NH:14][C:13]([C:15]2[CH:20]=[CH:19][C:18]([Cl:21])=[CH:17][CH:16]=2)=[N:12][CH:11]=[C:10]1[CH3:22].C1(P(C2CCCCC2)C2C=CC=CC=2C2C(C(C)C)=CC(C(C)C)=CC=2C(C)C)CCCCC1.[O-]P([O-])([O-])=O.[K+].[K+].[K+]>C(OCC)(=O)C.Cl.C([O-])(=O)C.[Pd+2].C([O-])(=O)C.O1CCOCC1>[Cl:21][C:18]1[CH:17]=[CH:16][C:15]([C:13]2[N:12]=[C:11]([CH:5]3[C:3](=[O:4])[CH2:2][CH2:1][C:6]3=[O:7])[C:10]([CH3:22])=[CH:9][N:14]=2)=[CH:20][CH:19]=1

Participants

9

Reactant 4

HCID 62657Potassium Phosphate, TribasicHCID 774661,3-CyclopentanedioneHCID 111557942-Dicyclohexylphosphino-2',4',6'-triisoprophylbiphenylHCID 178430308HCID 178430308, compound

Product 1

HCID 669261742-[2-(4-Chloro-phenyl)-5-methyl-pyrimidin-4-yl]-cyclopentane-1,3-dioneYield 27%

Reagents, catalysts & solvents 4

HCID 167845palladium(II) acetateCatalystHCID 313Hydrochloric AcidSolventHCID 8857Ethyl AcetateSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
150 °C

Procedure

To a microwave vial was added 1,3-cyclopentadione (0.5 g, 5.1 mmol), 6-Chloro-2-(4-chloro-phenyl)-5-methyl-1,6-dihydro-pyrimidine (1.04 g, 4.3 mmol), palladium acetate (58 mg, 0.26 mmol), 2-Dicyclohexylphosphino-2′,4′,6′-triisopropylbiphenyl (183 mg, 0.38 mmol), potassium phosphate tribasic (2.49 g, 11.7 mmol) and 1,4-dioxane (10 ml). This was heated in the microwave for 30 minutes at 150° C. on a normal setting with a pre-stir of 25 seconds. The resulting slurry was diluted with ethyl acetate (10 ml) and 2M hydrochloric acid (10 ml) before filtering through celite. The filter cake was washed with further ethyl acetate (10 ml) and 2M hydrochloric acid (10 ml). The resulting biphasic mixture was separated and the aqueous layer was extracted with further ethyl acetate (2×10 ml). The combined organic layers were then dried with magnesium sulphate, filtered and stripped to dryness to yield a dark yellow solid. This was purified by normal phase chromatography (gradient system of 100% dichloromethane−5% methanol:dichloromethane) to give 2-[2-(4-Chloro-phenyl)-5-methyl-pyrimidin-4-yl]-cyclopentane-1,3-dione as a yellow solid (348 mg, 1.16 mmol, 22% yield).

Workup

  1. filtrationbefore filtering through celite
  2. washThe filter cake was washed with further ethyl acetate (10 ml) and 2M hydrochloric acid (10 ml)
  3. customThe resulting biphasic mixture was separated
  4. extractionthe aqueous layer was extracted with further ethyl acetate (2×10 ml)
  5. dry with materialThe combined organic layers were then dried with magnesium sulphate
  6. filtrationfiltered
  7. customto yield a dark yellow solid
  8. customThis was purified by normal phase chromatography (gradient system of 100% dichloromethane−5% methanol:dichloromethane)

Sources & evidence

ORD record
ord-96e9133076d141f8ba4d650d27ce71aa
Source dataset
uspto-grants-2015_06
Patent number
US09051300B2

Reaction notes

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