3-Acetyl-6-methylpyridine → 1-(6-Methylpyridin-3-yl)-2-(4-(methylsulfonyl)phenyl)ethanone

HRID 1183784Notes

Reaction equation

HRID 1183784 reaction equation
C([PH+]([C:10]([CH3:13])([CH3:12])C)C(C)(C)C)(C)(C)C.BrC1C=C[C:18]([CH2:21][S:22]([CH2:25]C2C=CC(Br)=CC=2)(=[O:24])=[O:23])=[CH:17]C=1.[CH3:33][C:34]1[N:39]=[CH:38][C:37]([C:40](=[O:42])[CH3:41])=[CH:36][CH:35]=1>C([O-])(O)=O.[Na+].CC([O-])=O.CC([O-])=O.[Pd+2]>[CH3:33][C:34]1[N:39]=[CH:38][C:37]([C:40](=[O:42])[CH2:41][C:12]2[CH:10]=[CH:13][C:21]([S:22]([CH3:25])(=[O:24])=[O:23])=[CH:18][CH:17]=2)=[CH:36][CH:35]=1

Participants

6

Reactant 3

HCID 952923-Acetyl-6-methylpyridineHCID 2674191,1'-[Sulfonylbis(methylene)]bis(4-bromobenzene)HCID 4060964Tri-t-butylphosphonium

Product 1

HCID 99259911-(6-Methylpyridin-3-yl)-2-(4-(methylsulfonyl)phenyl)ethanoneYield 30%

Reagents, catalysts & solvents 2

HCID 167845palladium(II) acetateCatalystHCID 516892Sodium BicarbonateSolvent

Conditions

Temperature
80 °C

Procedure

A Schlenk reaction tube anhydrified beforehand provided with magnetic anchor was loaded with tri-tert-butyl-phosphonium tetrafluoborate (5.4 mg; 18.5 μmol), Pd(OAc)2 (2.1 mg; 9.2 μmol), 4-bromophenylmethylsulfone (130.4 mg; 0.55 mmol), 1-(6-methylpyridin-3-yl)ethanone of formula (II) (50 mg; 0.37 mmol) and was closed with a septum. The vessel was degassed by 3 argon cycles, then 2 ml anhydrous toluene were added with a syringe. T-BuOK (165.7 mg; 1.48 mmol) was added in portions and the solution was heated to 80° C. for 16 hours. The mixture was diluted with a saturated solution of NaHCO3 (20 mL) and extracted with AcOEt (3×20 mL). The combined organic phases were washed with an aqueous solution saturated with NaHCO3 (20 mL), anhydrified on MgSO4 and concentrated in a vacuum. The residue was purified by flash chromatography using AcOEt/cyclohexane as eluent in a gradient from 5:5 to 10:0. 32.1 mg product were obtained, for a molar yield of 30% as a white crystalline solid.

Workup

  1. customA Schlenk reaction tube anhydrified
  2. custombeforehand provided with magnetic anchor
  3. customwas closed with a septum
  4. customThe vessel was degassed by 3 argon cycles
  5. addition2 ml anhydrous toluene were added with a syringe
  6. extractionextracted with AcOEt (3×20 mL)
  7. washThe combined organic phases were washed with an aqueous solution saturated with NaHCO3 (20 mL)
  8. concentrationconcentrated in a vacuum
  9. customThe residue was purified by flash chromatography

Sources & evidence

ORD record
ord-24723a1eb10d405e917d5b0dc196b56b
Source dataset
uspto-grants-2014_03
Patent number
US08664402B2

Reaction notes

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