反应详情

A solution of 4-benzyloxy-2-fluoro-benzamidine hydrochloride (74.5 g, 0.265 mol) in THF (705 mL) was treated with potassium hydrogen carbonate (106 g, 1.06 mol) and H2O (150 mL). The resultant mixture was heated to reflux to give a white suspension. Whilst maintaining gentle reflux and mechanical stirring (500 rpm) a solution of 2-chloro-1-(2-isopropyl-2H-[1,2,4]triazol-3-yl)-ethanone (50 g, 0.265 mol) was added dropwise over 40 min. The resultant suspension gradually dissolved giving a dark red mixture that was refluxed for 18 h. The mixture was cooled to RT, diluted with saturated aqueous NaCl solution (500 mL) and extracted with EtOAc (500 mL). The organic extract was washed with saturated aqueous NaCl solution, dried over Na2SO4, filtered and concentrated in vacuo to give a pink solid The solid was triturated in a mixture of MTBE/pentane (1:1 by volume, 300 mL), collected by filtration, washed with a MTBE/pentane mixture and dried in vacuo to give 5-[2-(4-Benzyloxy-2-fluoro-phenyl)-1H-imidazol-4-yl]-1-isopropyl-1H-[1,2,4]triazole as a pale pink solid (84 g, 84%). 1H NMR (400 MHz, d6-DMSO): 7.95-7.93 (2 H, m), 7.76 (1 H, s), 7.44-7.42 (5 H, m), 7.12 (1 H, dd, J=13.10, 2.52 Hz), 7.03 (1 H, dd, J=8.74, 2.47 Hz), 5.90 (1 H, m), 5.21 (2 H, s), 1.46 (6 H, d, J=6.60 Hz).

1. temperatureto reflux
2. customto give a white suspension
3. temperatureWhilst maintaining gentle
4. temperaturereflux
5. additionwas added dropwise over 40 min
6. customgiving a dark red mixture that
7. temperaturewas refluxed for 18 h
8. extractionextracted with EtOAc (500 mL)
9. extractionThe organic extract
10. washwas washed with saturated aqueous NaCl solution
11. dry with materialdried over Na2SO4
12. filtrationfiltered
13. concentrationconcentrated in vacuo
14. customto give a pink solid The solid
15. customwas triturated in a mixture of MTBE/pentane (1:1 by volume, 300 mL)
16. filtrationcollected by filtration
17. washwashed with a MTBE/pentane mixture
18. customdried in vacuo