Reaction #93191

Reaction equation

imidazole

3-Acetylthio-2-methylpropanoic acid

1,1'-carbonyldiimidazole

Glycolic acid

glycolic acid

→

O-[3-(Acetylthio)-2-methylpropanoyl]glycolic Acid

Solvents

tetrahydrofuran

tetrahydrofuran

triethylamine

Conditions

Workup

1. 1
   workup.WAITAfter several minutes
2. 2
   workup.WAITto run overnight at room temperature
3. 3
   FiltrationThe crystalline salt is filtered
4. 4
   Concentrationthe filtrate concentrated to dryness in vacuo
5. 5
   Washwashed with 1N hydrochloric acid and three times with water
6. 6
   Dryingdried over magnesium sulfate
7. 7
   Concentrationconcentrated to dryness in vacuo
8. 8
   workup.DISSOLUTIONby dissolving in ether/hexane
9. 9
   Otherprecipitating by the addition of dicyclohexylamine
10. 10
    OtherThe salt is recrystallized from ether, m.p. 120°-122°
11. 11
    workup.ADDITIONby adding to ethyl acetate
12. 12
    workup.ADDITIONadding 10% potassium bisulfate solution
13. 13
    Othercrystallizing from ethyl/hexane, yield 2.96 g

Procedure

3-Acetylthio-2-methylpropanoic acid (6.48 g) is taken into 40 ml of dry tetrahydrofuran. To this 1,1'-carbonyldiimidazole (0.48 g) is added and stirred for 30 minutes at room temperature. Glycolic acid (6.08 g) and 11.2 ml of triethylamine in 60 ml of dry tetrahydrofuran are added. After several minutes, the imidazole salt of glycolic acid begins to come out of solution. The reaction is permitted to run overnight at room temperature. The crystalline salt is filtered and the filtrate concentrated to dryness in vacuo. The residue is taken up into ethyl acetate, washed with 1N hydrochloric acid and three times with water, dried over magnesium sulfate and concentrated to dryness in vacuo. This product is converted to its dicyclohexylamine salt by dissolving in ether/hexane and precipitating by the addition of dicyclohexylamine. The salt is recrystallized from ether, m.p. 120°-122°. This salt is then converted to the free acid, O-[3-(acetylthio)-2-methylpropanoyl]glycolic acid by adding to ethyl acetate, adding 10% potassium bisulfate solution, then crystallizing from ethyl/hexane, yield 2.96 g., m.p. 50°-51°.

Source