1,1'-Carbonyldiimidazole → N-[4-(2-Fluorophenylcarbonyl)phenyl]-3,3,3-trifluoro-2-hydroxy-2-trifluoromethylpropanamide

To a stirred solution of 3,3,3-trifluoro-2-hydroxy-2-trifluoromethylpropanoic acid (1.17 g, 5.5 mmol) in dry tetrahydrofuran (35 mL) was added 1,1'-carbonyldiimidazole (0.89 g, 5.5 mmol). The mixture was heated at reflux for 45 minutes, then cooled to room temperature. 4-Amino-2'-fluorobenzophenone (1.08 g, 5.0 mmol) was added in one portion and the reaction mixture heated at reflux for 48 hours. Tetrahydrofuran was removed from the reaction mixture in vacuo, and the residue dissolved in ethyl ether and filtered. The filtrate was washed with 3N HCl (50 mL) and water. The ether extract was dried (MgSO4) and concentrated in vacuo to an off-white solid which was purified by flash column chromatography (5% v/v ethyl ether/methylene chloride). Recrystallization of the resulting solid from hexane yielded the title propanamide as a tan solid (0.83 g, 40%); mp 137°-139° C. 1H-NMR (300 MHz, d6 -DMSO): 7.36-7.42 (m, 2H, aromatic) 7.54-7.60 (m, 1H, aromatic) 7.63-7.69 (m, 1H, aromatic) 7.76-7.79 (m, 2H, aromatic) 7.92-7.96 (m, 2H, aromatic) 9.84 (s, 1H, NH) 10.86 (bs, 1H, OH). MS (CI, CH4): 410 (M+1).

1. temperatureThe mixture was heated
2. temperatureat reflux for 45 minutes
3. temperaturethe reaction mixture heated
4. temperatureat reflux for 48 hours
5. customTetrahydrofuran was removed from the reaction mixture in vacuo
6. dissolutionthe residue dissolved in ethyl ether
7. filtrationfiltered
8. washThe filtrate was washed with 3N HCl (50 mL) and water
9. extractionThe ether extract
10. dry with materialwas dried (MgSO4)
11. concentrationconcentrated in vacuo to an off-white solid which
12. customwas purified by flash column chromatography (5% v/v ethyl ether/methylene chloride)
13. customRecrystallization of the resulting solid from hexane

ORD record

ord-bd9d21b9ecb14522aaf2623b5c3aaaab

Source dataset

uspto-grants-1995_01

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US05382598