Reaction #76439

Reaction equation

N-(4-chloro-3-methylisothiazol-5-yl)-2-(3-amino-4-hydroxyphenyl)propionamide

3,3,3-trifluoropropionic acid

1-(3-diethylaminopropyl)-3-ethylcarbodiimide hydrochloride

→

N-(4-chloro-3-methylisothiazol-5-yl)-2-[4-hydroxy-3-(3,3,3-trifluoropropionamido)phenyl]propionamide

Yield 73.5%

Solvents

N,N-dimethylacetamide

Conditions

Workup

1. 1
   OtherThe reaction was quenched with water
2. 2
   Extractionextracted with ethyl acetate
3. 3
   ExtractionThe organic extract
4. 4
   Washwas washed with water
5. 5
   Dryingdried over anhydrous magnesium sulfate
6. 6
   Filtrationfiltered
7. 7
   Otherthe filtrate was evaporated in vacuo
8. 8
   OtherThe residue was purified by flash column chromatography on silica gel
9. 9
   Washeluting with ethyl acetate:hexane 1:1

Procedure

A mixture of N-(4-chloro-3-methylisothiazol-5-yl)-2-(3-amino-4-hydroxyphenyl)propionamide (0.65 g, 0.002 mol), 3,3,3-trifluoropropionic acid (0.267 g, 0.002 mol) and 1-(3-diethylaminopropyl)-3-ethylcarbodiimide hydrochloride (0.40 g, 0.002 mol) was stirred in N,N-dimethylacetamide (8 ml) at room temperature for 7 hours and was then allowed to stand at room temperature overnight. The reaction was quenched with water and extracted with ethyl acetate. The organic extract was washed with water, dried over anhydrous magnesium sulfate, filtered and the filtrate was evaporated in vacuo. The residue was purified by flash column chromatography on silica gel, eluting with ethyl acetate:hexane 1:1, to give N-(4-chloro-3-methylisothiazol-5-yl)-2-[4-hydroxy-3-(3,3,3-trifluoropropionamido)phenyl]propionamide (0.62 g) as a white solid.

Source