反应详情

A solution of 2-bromo-4-trifluoromethylpyridine (1.00 g, 4.42 mmol), tert-butyl piperidine-4-ylcarbamate (0.93 g, 4.65 mmol) and TEA (0.67 mL, 4.86 mmol) in DMSO (5 L) was heated at 120° C. for 17 h. The reaction mixture was evaporated to dryness, Et2O was added, and the organic phase was washed with water, brine and evaporated to dryness. The residue was purified using the Biotage Horizon HPFC system eluting with 22% EtOAc in petroleum ether (40-60° C.) to give the title compound (1.08 g, 71%) as a solid. 1H NMR (500 MHz, CDCl3): 8.30 (d, 1H), 6.82 (s, 1H), 6.77 (d, 1H), 4.49 (bs, 1H), 4.36-4.22 (m, 2H), 3.74 (bs, 1H), 3.06 (td, 2H), 2.10-2.04 (m, 2H), 1.56-1.38 (m, 11H); 13C NMR (CDCl3): 159.4, 155.4, 149.5, 140.1, 139.9, 124.5, 122.4, 108.1, 102.7, 79.8, 48.3, 44.4, 32.3, 28.6; Mass Spectrum: M+H 346.

1. customThe reaction mixture was evaporated to dryness, Et2O
2. additionwas added
3. washthe organic phase was washed with water, brine
4. customevaporated to dryness
5. customThe residue was purified
6. washeluting with 22% EtOAc in petroleum ether (40-60° C.)