反应详情

温度

67 °C

To a mixture of Methanol (66 L) and Water (10 L) at 20° C. was added purified (R)-5-(2-(benzylamino)ethyl)-1-(6,8-difluorochroman-3-yl)-1H-imidazole-2(3H)-thione hydrochloride (4.37 kg, 9.98 mol) to afford a suspension. The reaction mixture was then heated to 67° C. to affect complete dissolution, whereupon 1N Sodium hydroxide (10.48 L, 10.48 mol, 1.05 eq) was added in a single portion. The reaction mixture was adjusted back to 67° C. and held at 67° C. for 30 min. The reaction mixture was then cooled to 20° C. and aged at 20° C. for at least 30 min. The reaction was then filtered and the filter cake washed with aqueous Methanol (1:1 v/v, 20 L), sucked down for 15 min. and then dried at 45° C. under vacuum, to afford (R)-5-(2-(benzylamino)ethyl)-1-(6,8-difluorochroman-3-yl)-1H-imidazole-2(3H)-thione (3.855 kg, 96%) as a pale tan crystalline solid.

1. additionwas added
2. customto afford a suspension
3. dissolutiondissolution
4. customwas adjusted back to 67° C.
5. temperatureThe reaction mixture was then cooled to 20° C.
6. waitaged at 20° C. for at least 30 min
7. filtrationThe reaction was then filtered
8. washthe filter cake washed with aqueous Methanol (1:1 v/v, 20 L)
9. waitsucked down for 15 min.
10. customdried at 45° C. under vacuum