1-Bromo-4-(methylsulphonyl)benzene → 1-(6-Methylpyridin-3-yl)-2-(4-(methylsulfonyl)phenyl)ethanone

HRID 1617335Notes

Reaction equation

HRID 1617335 reaction equation
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.O.O.O.P([O-])([O-])([O-])=O.[K+].[K+].[K+].[CH3:54][S:55]([C:58]1[CH:63]=[CH:62][C:61](Br)=[CH:60][CH:59]=1)(=[O:57])=[O:56].[C:65]([C:68]1[CH:69]=[CH:70][C:71]([CH3:74])=[N:72][CH:73]=1)(=[O:67])[CH3:66]>O.C([O-])(=O)C.[Pd+2].C([O-])(=O)C>[CH3:74][C:71]1[N:72]=[CH:73][C:68]([C:65](=[O:67])[CH2:66][C:61]2[CH:62]=[CH:63][C:58]([S:55]([CH3:54])(=[O:57])=[O:56])=[CH:59][CH:60]=2)=[CH:69][CH:70]=1

Participants

7

Reactant 4

HCID 770141-Bromo-4-(methylsulphonyl)benzeneHCID 952923-Acetyl-6-methylpyridineHCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)HCID 18407952Tripotassium phosphate trihydrate

Product 1

HCID 99259911-(6-Methylpyridin-3-yl)-2-(4-(methylsulfonyl)phenyl)ethanoneYield 90.1%

Reagents, catalysts & solvents 2

HCID 167845palladium(II) acetateCatalystHCID 962WaterSolvent2×

Conditions

Temperature
87.5 °C

Procedure

To a four-neck round-bottom 250 ml flask equipped with mechanical stirring and condenser were added at 20-25° C. and under nitrogen atmosphere Xantphos, palladium acetate, tripotassium phosphate trihydrate, PVP, 4-bromophenyl methyl sulfone, 5-acetyl-2-methyl pyridine, water (50.00 ml). A vacuum/nitrogen cycle was repeated for at least three times at 20-25° C. The resulting reaction mixture was heated up to 85-90° C. and stirred for at least 24 h. The reaction mixture was transferred in an other recipient then cooled down to 40-50° C. and diluted with water (400 ml). The resulting mixture was stirred at 40-45° C. for 15 min and cooled down to −5-0° C. The resulting reaction mixture was stirred at −5-0° C. for at least 2 h, then it was filtered and the cake was washed with water (3×100 ml) and dried at 65-70° C. under reduced pressure to afford a crude product of formula (I) as a yellow solid (48.3 g). yield: 90.1%, Purity: 75.7% by HPLC A %.

Workup

  1. customTo a four-neck round-bottom 250 ml flask equipped
  2. customwas repeated for at least three times at 20-25° C
  3. customThe resulting reaction mixture
  4. stirringstirred for at least 24 h
  5. temperaturethen cooled down to 40-50° C.
  6. stirringThe resulting mixture was stirred at 40-45° C. for 15 min
  7. temperaturecooled down to −5-0° C
  8. customThe resulting reaction mixture
  9. stirringwas stirred at −5-0° C. for at least 2 h
  10. filtrationit was filtered
  11. washthe cake was washed with water (3×100 ml)
  12. customdried at 65-70° C. under reduced pressure

Sources & evidence

ORD record
ord-f0e869c8136a4f2b90abacdf172d0455
Source dataset
uspto-grants-2014_07
Patent number
US08765962B1

Reaction notes

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