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

HRID 1297176Notes

Reaction equation

HRID 1297176 reaction equation
C(O[C:4](=[O:13])[CH:5]=[C:6](OC)[C:7]([F:10])([F:9])[F:8])C.[C:14]([O:18][CH3:19])(=[O:17])[CH2:15][SH:16].[OH-].[K+].OS(O)(=O)=O>CO.O>[CH3:19][O:18][C:14]([C:15]1[S:16][C:6]([C:7]([F:8])([F:9])[F:10])=[CH:5][C:4]=1[OH:13])=[O:17]

Participants

7

Reactant 4

HCID 1118Sulfuric AcidHCID 14797Potassium HydroxideHCID 16907Methyl ThioglycolateHCID 27588673-Methoxy-4,4,4-trifluoro-2-butenoic acid ethyl ester

Product 1

HCID 2759855Methyl 3-hydroxy-5-(trifluoromethyl)thiophene-2-carboxylateYield 91.2%

Reagents, catalysts & solvents 2

HCID 887MethanolSolvent2×HCID 962WaterSolvent

Procedure

A solution of 4,4,4-trifluoro-3-methoxy-but-2-enoic acid ethyl ester (9.6 g, 48.5 mmol) and methyl thioglycolate (4.3 mL, 48.5 mmol) in MeOH (75 mL) is cooled to 5° C. A solution of KOH (3.3 g, 58.2 mmol) in MeOH (75 mL) is then added over 30 min. The reaction mixture is stirred overnight at room temperature. The reaction mixture is then poured over a stirred mixture of ice (75 g), H2O (75 mL) and concentrated H2SO4 (4.5 mL). The mixture is extracted with EtOAc (2×250 mL). The combined extracts are washed with saturated NaHCO3. The washings are back-extracted with EtOAc. The combined organic layers are washed with brine, then dried (Na2SO4), filtered and concentrated to afford the title compound (10 g, 91%) as a brown oil which is used without further purification.

Workup

  1. extractionThe mixture is extracted with EtOAc (2×250 mL)
  2. washThe combined extracts are washed with saturated NaHCO3
  3. extractionThe washings are back-extracted with EtOAc
  4. washThe combined organic layers are washed with brine
  5. dry with materialdried (Na2SO4)
  6. filtrationfiltered
  7. concentrationconcentrated

Sources & evidence

ORD record
ord-e85241ecff4c44df851e7e7b2fa9ae62
Source dataset
uspto-grants-2007_07
Patent number
US07250430B2

Reaction notes

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