Potassium Phosphate, Tribasic → 3-[3-(4-Chlorophenyl)-6-methylphenyl]-5,5-dimethylpyrrolidine-2,4-dione

HRID 918994Notes

Reaction equation

HRID 918994 reaction equation
C(P(C(C)(C)C)C1C=CC=CC=1C1C=CC=CC=1C)(C)(C)C.[O-]P([O-])([O-])=O.[K+].[K+].[K+].[CH3:31][C:32]1([CH3:39])[NH:36][C:35](=[O:37])[CH2:34][C:33]1=[O:38].[Cl:40][C:41]1[CH:46]=[CH:45][C:44]([C:47]2[CH:48]=[C:49](Br)[C:50]([CH3:53])=[CH:51][CH:52]=2)=[CH:43][CH:42]=1>O1CCOCC1.CO>[Cl:40][C:41]1[CH:42]=[CH:43][C:44]([C:47]2[CH:52]=[C:51]([CH:34]3[C:33](=[O:38])[C:32]([CH3:39])([CH3:31])[NH:36][C:35]3=[O:37])[C:50]([CH3:53])=[CH:49][CH:48]=2)=[CH:45][CH:46]=1

Participants

7

Reactant 4

HCID 62657Potassium Phosphate, TribasicHCID 27349372-(Di-tert-butylphosphino)-2'-methyl-1,1'-biphenylHCID 133467095,5-Dimethylpyrrolidine-2,4-dioneHCID 594459301-Bromo-5-(4-chlorophenyl)-2-methylbenzene

Product 1

HCID 704963423-[3-(4-Chlorophenyl)-6-methylphenyl]-5,5-dimethylpyrrolidine-2,4-dione

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 312751,4-DioxaneSolvent

Procedure

Under argon, in a heat-dried apparatus, 7.4 mg of Pd(OAc), 22 mg of di-tert-butyl(2′-methylbiphenyl-2-yl)phosphine and 0.78 g of K3PO4 in 4.8 ml of air-free dioxane are introduced as initial charge. 203 mg of 5,5-dimethylpyrrolidine-2,4-dione and 659 mg of 3-(4-chlorophenyl)-6-methylbromobenzene are added and the mixture is stirred for 16 hours under reflux. The mixture is 10 then left to cool to room temperature, diluted with ca. 6 ml of methanol and filtered, and the filter residue is after-washed with ca. 3 ml of MeOH. The combined filtrates are concentrated by evaporation on a rotary evaporator. The residue is taken up in ca. 6 ml of water and rendered weakly acidic using 1 N hydrochloric acid. The precipitated solid is filtered off with suction and washed with ca. 3 ml of water. It is then washed from the filter with acetone and the filtrate is concentrated by evaporation. This gives 0.597 g of solid. Reversed-phase separation with water/acetonitrile (gradient) gives 93 mg (14% of theory) with a purity of 98.6% according to HPLC/MS.

Workup

  1. additionas initial charge
  2. temperatureunder reflux
  3. waitthen left
  4. filtrationfiltered
  5. washthe filter residue is after-washed with ca. 3 ml of MeOH
  6. concentrationThe combined filtrates are concentrated by evaporation on a rotary evaporator
  7. filtrationThe precipitated solid is filtered off with suction
  8. washwashed with ca. 3 ml of water
  9. washIt is then washed from the
  10. filtrationfilter with acetone
  11. concentrationthe filtrate is concentrated by evaporation
  12. customReversed-phase separation with water/acetonitrile (gradient)
  13. customgives 93 mg (14% of theory) with a purity of 98.6%

Sources & evidence

ORD record
ord-98a009592bd14e95b24237c41b3ca74c
Source dataset
uspto-grants-2016_03
Patent number
US09272997B2

Reaction notes

Loading…