反应详情

温度

50 °C

A mixture of (R)-2-chloro-4-nitro-1-(2-methyl-2-oxiranylmethyl)imidazole (3 g, 13.79 mmol), tert-butyl 4-piperazin-1-yl-piperidine-1-carboxylate (3.9 g, 14.48 mmol), and ethanol (30 ml) was stirred at 50° C. for 9 hours. The reaction mixture was concentrated, and the residue was purified by silica gel column chromatography (methylene chloride/methanol=10/1) to obtain a yellow amorphous form. The amorphous form was dissolved in N,N-dimethylformamide (18 ml), sodium hydride (651 mg, 16.28 mmol) was added while cooling on ice, and the resultant solution was stirred at the same temperature for 1 hour. To the reaction mixture, ethyl acetate (6 ml) and water (42 ml) were added in this order, and the precipitated crystals were filtered off and washed with water. The filtrate was recrystallized from 2-propanol (20 ml)/water (60 ml) to obtain tert-butyl (S)-4-[4-(2-methyl-6-nitro-2,3-dihydroimidazo[2,1-b]oxazol-2-ylmethyl)piperazin-1-yl]piperidine-1-carboxylate (4.08 g, 66%) as a light yellow powder.

1. concentrationThe reaction mixture was concentrated
2. customthe residue was purified by silica gel column chromatography (methylene chloride/methanol=10/1)
3. customto obtain a yellow amorphous form
4. temperaturewhile cooling on ice
5. filtrationthe precipitated crystals were filtered off
6. washwashed with water
7. customThe filtrate was recrystallized from 2-propanol (20 ml)/water (60 ml)