Cesium carbonate → 2-((3,5-Difluoro-4-nitrophenoxy)methyl)-5-methylpyridine

HRID 1527725Notes

Reaction equation

HRID 1527725 reaction equation
[F:1][C:2]1[CH:3]=[C:4]([OH:12])[CH:5]=[C:6]([F:11])[C:7]=1[N+:8]([O-:10])=[O:9].C([O-])([O-])=O.[Cs+].[Cs+].Cl.Cl[CH2:21][C:22]1[CH:27]=[CH:26][C:25]([CH3:28])=[CH:24][N:23]=1.C([O-])(O)=O.[Na+]>CN(C=O)C>[F:1][C:2]1[CH:3]=[C:4]([CH:5]=[C:6]([F:11])[C:7]=1[N+:8]([O-:10])=[O:9])[O:12][CH2:21][C:22]1[CH:27]=[CH:26][C:25]([CH3:28])=[CH:24][N:23]=1

Participants

6

Reactant 4

HCID 10796Cesium carbonateHCID 516892Sodium BicarbonateHCID 178437653,5-Difluoro-4-nitrophenolHCID 233137952-(Chloromethyl)-5-methylpyridine hydrochloride

Product 1

HCID 904102502-((3,5-Difluoro-4-nitrophenoxy)methyl)-5-methylpyridine

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
75 °C

Procedure

To 3,5-difluoro-4-nitrophenol (7.44 g, 42.5 mmol), Cs2CO3 (27.7 g, 84.9 mmol), and 2-(chloromethyl)-5-methylpyridine hydrochloride (7.6 g, 42.5 mmol) was added DMF (281 mL) and the reaction was stirred at 75° Celsius for 18 hours. The reaction was allowed to cool to room temperature before being poured into sat. NaHCO3. The aqueous phase was extracted three times with EtOAc, and the combined organic layers were washed four times with brine, dried (Na2SO4), filtered, and concentrated. The crude material was purified via FCC to afford the title compound. MS (ESI): mass calcd. for C13H10F2N2O3, 280.1; m/z found, 281.0 [M+H]+.

Workup

  1. temperatureto cool to room temperature
  2. extractionThe aqueous phase was extracted three times with EtOAc
  3. washthe combined organic layers were washed four times with brine
  4. dry with materialdried (Na2SO4)
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customThe crude material was purified via FCC

Sources & evidence

ORD record
ord-a37c3e915a26495bbac9cc5aa6dd7d30
Source dataset
uspto-grants-2015_07
Patent number
US09089569B2

Reaction notes

Loading…