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

HRID 1183785Notes

Reaction equation

HRID 1183785 reaction equation
C[C:2]1(C)[C:28]2[C:23](=[C:24](P(C3C=CC=CC=3)C3C=CC=CC=3)[CH:25]=[CH:26][CH:27]=2)O[C:4]2[C:5](P(C3C=CC=CC=3)C3C=CC=CC=3)=[CH:6][CH:7]=[CH:8][C:3]1=2.BrC1C=CC([CH2:50][S:51](CC2C=CC(Br)=CC=2)(=[O:53])=[O:52])=CC=1.C(C1[C:66](C)=[N:67]C=CC=1)(=O)C.[O-:72]P([O-])([O-])=O.[K+].[K+].[K+]>C/C(/[O-])=C/C(C)=O.C/C(/[O-])=C/C(C)=O.[Pd+2]>[CH3:27][C:26]1[N:67]=[CH:66][C:23]([C:28](=[O:72])[CH2:2][C:3]2[CH:4]=[CH:5][C:6]([S:51]([CH3:50])(=[O:53])=[O:52])=[CH:7][CH:8]=2)=[CH:24][CH:25]=1

Participants

6

Reactant 4

HCID 62657Potassium Phosphate, TribasicHCID 2674191,1'-[Sulfonylbis(methylene)]bis(4-bromobenzene)HCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)HCID 109424821-(2-Methylpyridin-3-yl)ethan-1-one

Product 1

HCID 99259911-(6-Methylpyridin-3-yl)-2-(4-(methylsulfonyl)phenyl)ethanoneYield 91%

Reagents, catalysts & solvents 1

HCID 5486778Palladium acetylacetonateCatalyst

Procedure

Pd(acac)2 (6.1 mg, 0.02 mmol, 0.5 mol %) and Xantphos (23.2 mg, 0.04 mmol, 1 mol o) are introduced into a flared flask provided with coolant. 4-bromophenylmethylsulfone of formula (III, X═Br) (1.17 g, 5 mmol), acetylpicoline of formula (II) (541 mg, 4 mmol) and K3PO4 (2.55 g, 12.0 mmol, 3 eq) are added thereto. Once the argon atmosphere has been stabilized with vacuum-argon cycles, anhydrous and degassed NMP (15 ml) is added with a syringe. The mixture is then kept stirred under stirring in an argon atmosphere for 18 h at 100° C. The conversion is quantitative. The reaction mixture is diluted with a saturated solution of NaHCO3 (50 mL) and extracted with AcOEt (4×50 mL). The combined organic phases were washed with an aqueous solution saturated with NaHCO3 (30 mL), anhydrified on MgSO4 and concentrated in a vacuum. The residue was purified by silica gel chromatography using AcOEt/cyclohexane as eluent in a gradient from 5:5 to 10:0. 1.05 g product were obtained, for a molar yield of 91% as a white crystalline solid.

Workup

  1. customprovided with coolant
  2. customanhydrous and degassed NMP (15 ml)
  3. additionis added with a syringe
  4. stirringunder stirring in an argon atmosphere for 18 h at 100° C
  5. additionThe reaction mixture is diluted with a saturated solution of NaHCO3 (50 mL)
  6. extractionextracted with AcOEt (4×50 mL)
  7. washThe combined organic phases were washed with an aqueous solution saturated with NaHCO3 (30 mL)
  8. concentrationconcentrated in a vacuum
  9. customThe residue was purified by silica gel chromatography

Sources & evidence

ORD record
ord-7bb0439871f54d4f9bda9c43562f240a
Source dataset
uspto-grants-2014_03
Patent number
US08664402B2

Reaction notes

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