2-Bromopyridine → 3-[2-Methoxy-5-(methylsulfonyl)-3-pyridinyl]-1-(3,4-dichlorophenyl)propan-1-one

HRID 280194Notes

Reaction equation

HRID 280194 reaction equation
Br[C:2]1[C:3]([O:12][CH3:13])=[N:4][CH:5]=[C:6]([S:8]([CH3:11])(=[O:10])=[O:9])[CH:7]=1.[CH:14]([CH:16]([C:18]1[CH:23]=[CH:22][C:21]([Cl:24])=[C:20]([Cl:25])[CH:19]=1)[OH:17])=[CH2:15].C(=O)(O)[O-].[Na+].BrC1C=CC=CN=1>C(OCC)(=O)C.C([O-])(=O)C.C([O-])(=O)C.[Pd+2].CN(C)C=O>[CH3:13][O:12][C:3]1[C:2]([CH2:15][CH2:14][C:16]([C:18]2[CH:23]=[CH:22][C:21]([Cl:24])=[C:20]([Cl:25])[CH:19]=2)=[O:17])=[CH:7][C:6]([S:8]([CH3:11])(=[O:10])=[O:9])=[CH:5][N:4]=1

Participants

8

Reactant 4

HCID 79732-BromopyridineHCID 516892Sodium BicarbonateHCID 135677643-Bromo-2-methoxy-5-(methylsulfonyl)pyridineHCID 135677651-(3,4-Dichlorophenyl)prop-2-en-1-ol

Product 1

HCID 135677663-[2-Methoxy-5-(methylsulfonyl)-3-pyridinyl]-1-(3,4-dichlorophenyl)propan-1-one

Reagents, catalysts & solvents 3

HCID 167845palladium(II) acetateCatalystHCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
120 °C

Procedure

A mixture of 2.7 g of 3-bromo-2-methoxy-5-(methylsulfonyl)pyridine, 3.1 g of α-ethenyl-3,4-dichlorobenzenemethanol, 1.3 g of sodium bicarbonate, 10 ml of dimethylformamide and 0.11 g of palladium diacetate was stirred under nitrogen and heated to 120° C. After 6 hours, thin layer chromatography showed no unreacted bromopyridine starting material. The mixture was then cooled, diluted with ethyl acetate and filtered through Celite. The ethyl acetate solution was washed with water and then twice with aqueous saturated sodium chloride solution and dried over magnesium sulfate. The solution was then filtered and concentrated to a black oil. Excess alcohol was removed by Kugelrohr distillation and the glassy residue was taken up in methylene chloride and chromatographed on silica gel to give a pale yellow solid. This was recrystallized from ethanol/ethyl acetate to give 3-[2-methoxy-5-(methylsulfonyl)-3-pyridinyl]-1-(3,4-dichlorophenyl)propan-1-one melting at about 145°-146° C.

Workup

  1. temperatureThe mixture was then cooled
  2. filtrationfiltered through Celite
  3. washThe ethyl acetate solution was washed with water
  4. dry with materialtwice with aqueous saturated sodium chloride solution and dried over magnesium sulfate
  5. filtrationThe solution was then filtered
  6. concentrationconcentrated to a black oil
  7. customExcess alcohol was removed by Kugelrohr distillation
  8. customchromatographed on silica gel
  9. customto give a pale yellow solid
  10. customThis was recrystallized from ethanol/ethyl acetate

Sources & evidence

ORD record
ord-a0dab8627a8e4aac9c45da328017640b
Source dataset
uspto-grants-1986_05
Patent number
US04588733

Reaction notes

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