1,1'-Carbonyldiimidazole → N-[4-(3-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-3'-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. Purification by flash column chromatography (5% v/v ethyl ether/methylene chloride) yielded the title propanamide as a tan solid (1.13 g, 55%); mp 169°-171° C. 1H-NMR (300 MHz, d6 -DMSO): 7.50-7.64 (m, 4H, aromatic) 7.77-7.82 (m, 2 H, aromatic) 7.94-7.98 (m, 2H, aromatic) 9.84 (s, 1H, NH) 10.85 (bs, 1H, OH). MS (CI, CH4): 410 (M+1). Analysis for C17H10F7NO3 : Calculated: C, 49.89; H, 2.46; N, 3.42. Found: C, 49.60; H, 2.43; N, 3.34.

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
12. customPurification by flash column chromatography (5% v/v ethyl ether/methylene chloride)

ORD record

ord-1a3a93147c454738a47fe8d8dd9c8047

Source dataset

uspto-grants-1995_12

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US05474999