Methyl Salicylate → HCID 57485433, compound

HRID 1437033Notes

Reaction equation

HRID 1437033 reaction equation
[OH:1][C:2]1[CH:11]=[CH:10][CH:9]=[CH:8][C:3]=1[C:4]([O:6]C)=O.[Br:12][C:13]1[CH:14]=[CH:15][C:16](F)=[C:17]([N+:19]([O-])=O)[CH:18]=1.C([O-])([O-])=O.[Cs+].[Cs+].C([O-])([O-])=O.[K+].[K+].[O-]S(S([O-])=O)=O.[Na+].[Na+].[H-].[Na+]>CN(C=O)C.CCOC(C)=O.C1(C)C=CC=CC=1.O.CCO>[Br:12][C:13]1[CH:14]=[CH:15][C:16]2[O:1][C:2]3[CH:11]=[CH:10][CH:9]=[CH:8][C:3]=3[C:4](=[O:6])[NH:19][C:17]=2[CH:18]=1

Participants

12

Reactant 6

HCID 4133Methyl SalicylateHCID 10796Cesium carbonateHCID 11430Potassium CarbonateHCID 24489Sodium DithioniteHCID 24758Sodium hydrideHCID 27363284-Bromo-1-fluoro-2-nitrobenzene

Product 1

HCID 57485433HCID 57485433, compoundYield 9%

Reagents, catalysts & solvents 5

HCID 702EthanolSolventHCID 962WaterSolventHCID 1140TolueneSolventHCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent2×

Conditions

Temperature
40 °C

Procedure

A mixture of a methyl 2-hydroxybenzoate (1.0 mL, 10.0 mmol), 5-bromo-2-fluoronitrobenzene (0.62 mL, 5.0 mmol) and Cs2CO3 (3.3 g, 10.0 mol) in DMF (12 mL) was stirred at 40° C. for 2 h. The mixture was diluted with EtOAc and washed with 2 M aqueous NaOH-solution. To the EtOAc-phase was added EtOH, H2O, K2CO3 (2.8 g, 20 mmol) and Na2S2O4 (3.5 g, 20 mmol) and the resulting mixture was stirred vigorously for 1 h. The aqueous phase was removed and the organic phase was washed with 1 M aqueous NaOH-solution and then concentrated. The residue was taken up in DMF (1 mL) and then toluene (4 mL) and NaH (60 mg, 1.5 mmol, 60% in mineral oil) were added and the resulting mixture was stirred at 80° C. over night, then quenched by addition of saturated aqueous NH4Cl-solution. The resulting mixture was diluted with EtOAc, washed with 2 M aqueous NaOH-solution, dried (Na2SO4), concentrated, filtered through a short SiO2-column, concentrated and crystallised from heptane:EtoAc to give 130 mg of the title compound (189JO56). MS (ESI) 290 (MH+). Purity for MH+ (UV/MS) 100/100.

Workup

  1. washwashed with 2 M aqueous NaOH-solution
  2. stirringthe resulting mixture was stirred vigorously for 1 h
  3. customThe aqueous phase was removed
  4. washthe organic phase was washed with 1 M aqueous NaOH-solution
  5. concentrationconcentrated
  6. stirringthe resulting mixture was stirred at 80° C. over night
  7. customquenched by addition of saturated aqueous NH4Cl-solution
  8. additionThe resulting mixture was diluted with EtOAc
  9. washwashed with 2 M aqueous NaOH-solution
  10. dry with materialdried (Na2SO4)
  11. concentrationconcentrated
  12. filtrationfiltered through a short SiO2-column
  13. concentrationconcentrated
  14. customcrystallised from heptane

Sources & evidence

ORD record
ord-44493a735f1f440c8f452dc8ec64311a
Source dataset
uspto-grants-2009_11
Patent number
US07622461B2

Reaction notes

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