Potassium Phosphate, Tribasic → 1-(6-Methylpyridin-3-yl)-2-(4-(methylsulfonyl)phenyl)ethanone

HRID 1183786Notes

Reaction equation

HRID 1183786 reaction equation
[CH3:1][C:2]1[N:7]=[CH:6][C:5]([C:8](=[O:10])[CH3:9])=[CH:4][CH:3]=1.Br[C:12]1[CH:17]=[CH:16][C:15]([S:18]([CH3:21])(=[O:20])=[O:19])=[CH:14][CH:13]=1.P([O-])([O-])([O-])=O.[K+].[K+].[K+].CC1(C)C2C(=C(P(C3C=CC=CC=3)C3C=CC=CC=3)C=CC=2)OC2C(P(C3C=CC=CC=3)C3C=CC=CC=3)=CC=CC1=2>C([O-])(=O)C.[Pd+2].C([O-])(=O)C.CN(C=O)C>[CH3:1][C:2]1[N:7]=[CH:6][C:5]([C:8](=[O:10])[CH2:9][C:12]2[CH:17]=[CH:16][C:15]([S:18]([CH3:21])(=[O:20])=[O:19])=[CH:14][CH:13]=2)=[CH:4][CH:3]=1

Participants

7

Reactant 4

HCID 62657Potassium Phosphate, TribasicHCID 770141-Bromo-4-(methylsulphonyl)benzeneHCID 952923-Acetyl-6-methylpyridineHCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)

Product 1

HCID 99259911-(6-Methylpyridin-3-yl)-2-(4-(methylsulfonyl)phenyl)ethanone

Reagents, catalysts & solvents 2

HCID 167845palladium(II) acetateCatalystHCID 6228DimethylformamideSolvent

Conditions

Temperature
25 °C

Procedure

1-(6-methylpyridin-3-yl)ethanone 1 (50 g, 370 mmol), 1-bromo-4-(methylsulfonyl)benzene 2 (87 g, 370 mmol), potassium phosphate (235.6 g, 3 equiv, 1.11 mol), palladium(II) acetate (125 mg, 0.15mol, 557 μmol), Xantphos (161 mg, 0.075% mol, 278 μmol) and N,N′-dimethylformamide (300 ml, 6 vol) were introduced in the order into a 2000 ml flask provided with mechanical stirring, thermometer and coolant, at 25° C. and under a nitrogen atmosphere. The reaction mixture was stirred at 25° C. and subject to three cycles of vacuum and nitrogen, then it was heated to 85° C. and stirred at such temperature for 27 h. The reaction mixture was then quenched to 45° C. and the stirring was stopped, promoting the separation of an aqueous phase that was removed by suction siphoning with the aid of vacuum. The resulting higher mixture was diluted with water (600 ml, 12 vol) and was quenched to 3° C. After 2 h stirring at such temperature, the resulting suspension was filtered and the product was washed with water (4×200 ml, 4×4 vol) and dried at 60° C. in vacuum, yielding the raw 1-(6-methylpyridin-3-yl)-2-[4-(methylsulfonyl)phenyl]ethanone of formula (I) (89.1 g, 83.2%) as a yellow solid.

Workup

  1. customprovided with mechanical stirring
  2. customcoolant, at 25° C. and under a nitrogen atmosphere
  3. temperatureit was heated to 85° C.
  4. stirringstirred at such temperature for 27 h
  5. customThe reaction mixture was then quenched to 45° C.
  6. customthe separation of an aqueous phase that
  7. customwas removed by suction
  8. additionThe resulting higher mixture was diluted with water (600 ml, 12 vol)
  9. customwas quenched to 3° C
  10. stirringAfter 2 h stirring at such temperature
  11. filtrationthe resulting suspension was filtered
  12. washthe product was washed with water (4×200 ml, 4×4 vol)
  13. customdried at 60° C. in vacuum

Sources & evidence

ORD record
ord-fda5f8b69e74467ba2c32fae7c447b66
Source dataset
uspto-grants-2014_03
Patent number
US08664402B2

Reaction notes

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