Potassium Fluoride → Methyl 4-bromo-5-(trifluoromethyl)thiophene-2-carboxylate

HRID 2392252Notes

Reaction equation

HRID 2392252 reaction equation
[Br:1][C:2]1[CH:3]=[C:4]([C:8]([O:10][CH3:11])=[O:9])[S:5][C:6]=1I.[F-:12].[K+].[F:14][C:15]([F:24])(S(F)(=O)=O)C(OC)=O>CN(C=O)C.CN(P(N(C)C)(N(C)C)=O)C.[Cu]I>[Br:1][C:2]1[CH:3]=[C:4]([C:8]([O:10][CH3:11])=[O:9])[S:5][C:6]=1[C:15]([F:24])([F:12])[F:14]

Participants

6

Reactant 3

HCID 522689Potassium FluorideHCID 547667Methyl 2,2-difluoro-2-(fluorosulfonyl)acetateHCID 57826852Methyl 4-bromo-5-iodothiophene-2-carboxylate

Product 1

HCID 57826561Methyl 4-bromo-5-(trifluoromethyl)thiophene-2-carboxylateYield 197%

Reagents, catalysts & solvents 2

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 19433458Dmf hmpaSolvent

Conditions

Temperature
70 °C

Procedure

To a solution of methyl 4-bromo-5-iodo-2-thiophenecarboxylate (500 mg, 1.44 mmol), copper (I) iodide (137 mg, 0.72 mmol) and potassium fluoride (251 mg, 4.32 mmol) in DMF/HMPA (5 ml/5 mL) was added methyl difluoro(fluorosulfonyl)acetate (1.1 g, 5.76 mmol). The mixture was heated at 70° C. under N2 in a sealed tube. After 1 h, the reaction was quenched with NH4Cl (sat'd) (2 mL), extracted with ether (5 mL×5) and washed with distilled water (5 mL×5). The combined organic phase was dried over Mg2SO4 and purified on silica (EtOAc/Hex, 20-50%) to afford the title compound (0.82 g) containing a 60% inseparable impurity: LC-MS m/z (ES) 290 (M+H)+.

Workup

  1. customthe reaction was quenched with NH4Cl (sat'd) (2 mL)
  2. extractionextracted with ether (5 mL×5)
  3. washwashed with distilled water (5 mL×5)
  4. dry with materialThe combined organic phase was dried over Mg2SO4
  5. custompurified on silica (EtOAc/Hex, 20-50%)

Sources & evidence

ORD record
ord-8bf377ca76df43e9806ed6e73fd75272
Source dataset
uspto-grants-2012_09
Patent number
US08273782B2

Reaction notes

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