Sulfuric Acid → Methyl 3-hydroxy-5-(trifluoromethyl)thiophene-2-carboxylate

HRID 1953962Notes

Reaction equation

HRID 1953962 reaction equation
CO[C:3]([C:10]([F:13])([F:12])[F:11])=[CH:4][C:5]([O:7]CC)=O.[C:14]([O:18][CH3:19])(=[O:17])[CH2:15][SH:16].[OH-].[K+].CO.OS(O)(=O)=O>CO>[OH:7][C:5]1[CH:4]=[C:3]([C:10]([F:11])([F:12])[F:13])[S:16][C:15]=1[C:14]([O:18][CH3:19])=[O:17]

Participants

6

Reactant 4

HCID 1118Sulfuric AcidHCID 16907Methyl ThioglycolateHCID 27588673-Methoxy-4,4,4-trifluoro-2-butenoic acid ethyl esterHCID 23689386Potassium hydroxide methanol

Product 1

HCID 2759855Methyl 3-hydroxy-5-(trifluoromethyl)thiophene-2-carboxylateYield 71%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

A solution of ethyl 3-methoxy-4,4,4-trifluoro-2-buteneoate (48.45 g, 0.245 mol) and methyl thioglycolate (25.95 g, 0.245 mole) in methanol is treated dropwise with 300 mL, 1M KOH/methanol over a 45 minute period at 35-42° C. (external cooling is used to control exotherm) and stirred at ambient temperatures until reaction is complete by GC analysis. The resultant reaction mixture is poured onto ice water, acidified with 6N H2SO4 to pH 2 and extracted with ethyl acetate. The ethyl acetate extracts are combined, washed sequentially with saturated NaHCO3 and brine, dried over MgSO4 and concentrated in vacuo to give a pale yellow liquid residue. The residue is vacuum distilled to give the title product as a clear liquid, 39.06 g (71% yield), bp 42-45° C./0.10 mm Hg, identified by 1HNMR, 13CNMR and 19FNMR analyses.

Workup

  1. temperature(external cooling is used to control exotherm)
  2. customThe resultant reaction mixture
  3. additionis poured onto ice water
  4. extractionextracted with ethyl acetate
  5. washwashed sequentially with saturated NaHCO3 and brine
  6. dry with materialdried over MgSO4
  7. concentrationconcentrated in vacuo
  8. customto give a pale yellow liquid residue
  9. distillationdistilled

Sources & evidence

ORD record
ord-e3772a9e8b254931bab90266fb23d631
Source dataset
uspto-grants-2000_09
Patent number
US06121202

Reaction notes

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