Reaction #1800

Reaction equation

methoxy-4-trifluoroethoxy-5-fluorobenzoate

NaOH

HCl

→

4-trifluoroethoxy-5-fluorobenzoic acid

Solvents

water

THF

water

Conditions

Workup

1. 1
   workup.ADDITIONwas dropped into the rapidly stirring solution at room temperature
2. 2
   OtherThe biphasic result
3. 3
   workup.ADDITIONwas added to the aqueous residue to a volume of 50 mL
4. 4
   ExtractionThe product was extracted with methylene chloride (3×50 mL)
5. 5
   ExtractionThe combined organics were extracted with brine (50 mL)
6. 6
   Dryingthe organic solvent was dried over MgSO4
7. 7
   Filtrationfiltered
8. 8
   Otherthe solvent was removed under reduced pressure

Procedure

The above methoxy-4-trifluoroethoxy-5-fluorobenzoate (420 mg, 1.7 mmol) was dissolved in freshly distilled THF (50 mL) and water was added (20 mL) and 2N NaOH (2 mL) was dropped into the rapidly stirring solution at room temperature. The solution was warmed to 50° C. and stirred rapidly for 18 hours. The biphasic result was reduced to a smaller volume under reduced pressure and water was added to the aqueous residue to a volume of 50 mL and was then acidified with 4 N HCl to a pH of 1-2. The product was extracted with methylene chloride (3×50 mL). The combined organics were extracted with brine (50 mL) and the organic solvent was dried over MgSO4 and filtered and the solvent was removed under reduced pressure to give the desired 4-trifluoroethoxy-5-fluorobenzoic acid.

Source