Dimethylformamide → 4-(benzyloxy)-1-(2-fluoro-4-(methylsulfonyl)phenyl)pyridin-2(1H)-one

HRID 1895706Notes

Reaction equation

HRID 1895706 reaction equation
[CH2:1]([O:8][C:9]1[CH:14]=[CH:13][NH:12][C:11](=[O:15])[CH:10]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.CN(C=O)C.[H-].[Na+].F[C:24]1[CH:29]=[CH:28][C:27]([S:30]([CH3:33])(=[O:32])=[O:31])=[CH:26][C:25]=1[F:34]>CCOC(C)=O.O>[CH2:1]([O:8][C:9]1[CH:14]=[CH:13][N:12]([C:24]2[CH:29]=[CH:28][C:27]([S:30]([CH3:33])(=[O:32])=[O:31])=[CH:26][C:25]=2[F:34])[C:11](=[O:15])[CH:10]=1)[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1

Participants

7

Reactant 4

HCID 6228DimethylformamideHCID 24758Sodium hydrideHCID 27827431,2-Difluoro-4-(methylsulfonyl)benzeneHCID 36077244-Benzyloxy-2(1H)-pyridone

Product 1

HCID 673677574-(benzyloxy)-1-(2-fluoro-4-(methylsulfonyl)phenyl)pyridin-2(1H)-oneYield 116.4%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8857Ethyl AcetateSolvent

Procedure

To 4-(benzyloxy)pyridin-2(1H)-one (6.12 g, 30.4 mmol) in a 500 mL recovery flask was applied vacuum for 5 minutes then placed under an atmosphere of nitrogen and added DMF (100 mL) to produce a suspension. Added NaH (60% in oil) (1.271 g, 31.8 mmol) over 10 minutes as a slow evolution of gas was observed. By 60 minutes, the tan suspension had become thicker and lighter in color. After 60 minutes added 1,2-difluoro-4-(methylsulfonyl)benzene (5.31 g, 27.6 mmol) and placed the reaction mixture in a 110° C. oil bath under nitrogen for 70 minutes to produce a tan suspension. Added 400 mL of water and 400 mL of EtOAc to the reaction, removed aqueous layer, washed organic layer with 400 mL of brine, dried with MgSO4, filtered and concentrated to give 12 g pale yellow powder. This was purified by flash chromatography (0.75-1.00% MeOH/CH2Cl2) followed by recrystallization from EtOAc to yield 5.39 g (14.4 mmol, 52% yield) of product as a white powder. MS (ESI) 374.4 (M+1).

Workup

  1. customto produce a suspension
  2. waitBy 60 minutes
  3. customin a 110° C.
  4. customfor 70 minutes
  5. customto produce a tan suspension
  6. customto the reaction
  7. customremoved aqueous layer
  8. washwashed organic layer with 400 mL of brine
  9. dry with materialdried with MgSO4
  10. filtrationfiltered
  11. concentrationconcentrated

Sources & evidence

ORD record
ord-8d1d4ebaac41464e82ff1e017621f686
Source dataset
uspto-grants-2013_08
Patent number
US08513424B2

Reaction notes

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