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

HRID 48161

Reaction equation

HRID 48161 reaction equation
[Cl:1][C:2]1[C:3]([CH3:20])=[N:4][S:5][C:6]=1[NH:7][C:8](=[O:19])[CH:9]([C:11]1[CH:16]=[CH:15][C:14]([OH:17])=[C:13]([NH2:18])[CH:12]=1)[CH3:10].[F:21][C:22]([F:28])([F:27])[CH2:23][C:24](O)=[O:25].Cl.C(N(CC)CCCN=C=NCC)C>CN(C)C(=O)C>[Cl:1][C:2]1[C:3]([CH3:20])=[N:4][S:5][C:6]=1[NH:7][C:8](=[O:19])[CH:9]([C:11]1[CH:16]=[CH:15][C:14]([OH:17])=[C:13]([NH:18][C:24](=[O:25])[CH2:23][C:22]([F:28])([F:27])[F:21])[CH:12]=1)[CH3:10]

Participants

5

Reactant 3

HCID 27779723,3,3-Trifluoropropionic acidHCID 99645121-(3-Diethylaminopropyl)-3-ethylcarbodiimide hydrochlorideHCID 22742099N-(4-chloro-3-methylisothiazol-5-yl)-2-(3-amino-4-hydroxyphenyl)propionamide

Product 1

HCID 22742118N-(4-chloro-3-methylisothiazol-5-yl)-2-[4-hydroxy-3-(3,3,3-trifluoropropionamido)phenyl]propionamideYield 73.5%

Reagents, catalysts & solvents 1

HCID 31374DimethylacetamideSolvent

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.

Workup

  1. customThe reaction was quenched with water
  2. extractionextracted with ethyl acetate
  3. extractionThe organic extract
  4. washwas washed with water
  5. dry with materialdried over anhydrous magnesium sulfate
  6. filtrationfiltered
  7. customthe filtrate was evaporated in vacuo
  8. customThe residue was purified by flash column chromatography on silica gel
  9. washeluting with ethyl acetate:hexane 1:1

Sources & evidence

ORD record
ord-4c9a56a369914b5eb3b3ecfbd160c61f
Source dataset
uspto-grants-2004_03
Patent number
US06703347B2

Linked notes

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