Dimethylformamide → Methyl 5-bromo-3-[(2,2-difluoroethyl)amino]thiophene-2-carboxylate

HRID 2364051Notes

Reaction equation

HRID 2364051 reaction equation
[Br:1][C:2]1[S:6][C:5]([C:7]([O:9][CH3:10])=[O:8])=[C:4]([NH:11][C:12](=O)[C:13](F)([F:15])[F:14])[CH:3]=1.FC(F)(F)S(OCC(F)F)(=O)=O.C(=O)([O-])[O-].[Cs+].[Cs+].CN(C=O)C>O>[Br:1][C:2]1[S:6][C:5]([C:7]([O:9][CH3:10])=[O:8])=[C:4]([NH:11][CH2:12][CH:13]([F:15])[F:14])[CH:3]=1

Participants

6

Reactant 4

HCID 6228DimethylformamideHCID 10796Cesium carbonateHCID 27740892,2-Difluoroethyl trifluoromethanesulfonateHCID 56965789Methyl 5-bromo-3-(2,2,2-trifluoroacetamido)thiophene-2-carboxylate

Product 1

HCID 86662297Methyl 5-bromo-3-[(2,2-difluoroethyl)amino]thiophene-2-carboxylateYield 64%

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Procedure

A mixture of methyl 5-bromo-3-[(trifluoroacetyl)amino]thiophene-2-carboxylate (500 mg, 1.51 mmol), 2,2-difluoroethyl trifluoromethanesulfonate (441 mg, 2.06 mmol), cesium carbonate (1.23 g, 3.78 mmol) and DMF (10 mL) was microwave-irradiated at 90° C. for 1 h. Then, water was added to quench the reaction. The organic materials were extracted with EtOAc. The combined extracts were washed with water and brine, dried over Na2SO4 and filtered. After removal of the solvent at reduced pressure, the residue was dissolved in MeOH (3 mL). To the solution were added potassium carbonate (100 mg) and water (1.5 mL). The mixture was stirred at room temperature for 0.5 h. After removal of the solvent at reduced pressure, the organic materials were extracted with EtOAc. The combined extracts were washed with brine, dried over Na2SO4 and filtered. After removal of the solvent at reduced pressure, the residue was purified by column chromatography (Purif, silica gel, hexane to 85:15 hexane/EtOAc) to give the title compound (290 mg, 64%) as a yellow solid:

Workup

  1. customwas microwave-irradiated at 90° C. for 1 h
  2. customto quench
  3. customthe reaction
  4. extractionThe organic materials were extracted with EtOAc
  5. washThe combined extracts were washed with water and brine
  6. dry with materialdried over Na2SO4
  7. filtrationfiltered
  8. customAfter removal of the solvent at reduced pressure
  9. dissolutionthe residue was dissolved in MeOH (3 mL)
  10. additionTo the solution were added potassium carbonate (100 mg) and water (1.5 mL)
  11. customAfter removal of the solvent at reduced pressure
  12. extractionthe organic materials were extracted with EtOAc
  13. washThe combined extracts were washed with brine
  14. dry with materialdried over Na2SO4
  15. filtrationfiltered
  16. customAfter removal of the solvent at reduced pressure
  17. customthe residue was purified by column chromatography (Purif, silica gel, hexane to 85:15 hexane/EtOAc)

Sources & evidence

ORD record
ord-5665869e23b046ee8d43b13335580285
Source dataset
uspto-grants-2014_04
Patent number
US08691828B2

Reaction notes

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