Reaction #7068

Reaction equation

4,4,4-trifluoro-3-methoxy-but-2-enoic acid ethyl ester

methyl thioglycolate

H2SO4

KOH

→

title compound

Yield 91.2%

3-Hydroxy-5-trifluoromethyl-thiophene-2-carboxylic acid methyl ester

Yield 91.2%

Solvents

MeOH

H2O

MeOH

Conditions

Workup

1. 1
   ExtractionThe mixture is extracted with EtOAc (2×250 mL)
2. 2
   WashThe combined extracts are washed with saturated NaHCO3
3. 3
   ExtractionThe washings are back-extracted with EtOAc
4. 4
   WashThe combined organic layers are washed with brine
5. 5
   Dryingdried (Na2SO4)
6. 6
   Filtrationfiltered
7. 7
   Concentrationconcentrated

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.

Source