反应详情

温度

160 °C

To a solution of 4-(2-(4-fluoro-3-(trifluoromethyl)phenyl)-2-oxoethylcarbamoyl)piperidine-1-carboxylic acid tert-butyl ester (29.4 g; 1.00 equiv; 67.99 mmol) in 1-butanol (150 mL; 1.64 mol), add ammonium acetate (15 equiv; 1.02 mol; 78.61 g) followed by TEA (1 equiv; 67.99 mmol; 9.48 mL). Stir the mixture at 160° C. in a sealed tube. After 3 h, cool to RT and partition between EA and water and wash the organic layer with water and brine. Concentrate in vacuo. Triturate the residue in MTBE, filter and dry in vacuo to give the title compound (18.23 g; 44.10 mmol; 64.86%) as a white solid. 1H NMR (300 MHz, DMSO): 12.01 (s, 1H), 8.08-8.04 (m, 2H), 7.70 (d, J=1.4 Hz, 1H), 7.49-7.43 (m, 1H), 3.99 (d, J=12.6 Hz, 2H), 2.92-2.85 (m, 3H), 1.91-1.87 (m, 2H), 1.64-1.51 (m, 2H), 1.41 (s, 9H).

1. temperaturecool to RT
2. custompartition between EA and water
3. washwash the organic layer with water and brine
4. concentrationConcentrate in vacuo
5. customTriturate the residue in MTBE
6. filtrationfilter
7. customdry in vacuo