反应详情

温度

50 °C

6-(7-Hydroxy-6,7-dihydro-5H-pyrrolo[1,2-c]imidazol-7-yl)-N-methyl-2-naphthamide (5.20 kg, 16.9 mol), ethanol (130 L) and activated carbon (260 g) were stirred at room temperature, and the insoluble material was filtered off, and washed with ethanol (15.6 L). The above-mentioned operations were repeated three times. The filtrates and washings were combined, and (2S,3S)-tartranilic acid (15.95 kg, 70.8 mol) and ethanol (20.8 L) were added thereto. The mixture was heated to about 50° C., allowed to cool to room temperature, stirred for about 4 hr, cooled to about 0° C., and stirred for about 1 hr. The precipitated crystals were collected by filtration, and washed with ethanol (31.2 L). The obtained wet crystals (about 23 kg) in ethanol (156 L) were stirred at room temperature for about 2 hr, and the mixture was cooled to about 0° C., and stirred for about 1 hr. The precipitated crystals were collected by filtration, and washed with ethanol (31.2 L). The obtained wet crystals (about 20 kg) were added to 1 mol/L aqueous sodium hydroxide solution (104 L), and the mixture was stirred at room temperature for about 1 hr. The precipitated crystals were collected by filtration, washed with water (93.6 L), and dried under reduced pressure to a constant amount to give 6-((7S)-hydroxy-6,7-dihydro-5H-pyrrolo[1,2-c]imidazol-7-yl)-N-methyl-2-naphthamide 1 hydrate (4.11 kg, 12.6 mol). yield 25%. containing 5.6 wt % water (by Karl-Fisher water measurement).

1. filtrationthe insoluble material was filtered off
2. washwashed with ethanol (15.6 L)
3. temperatureto cool to room temperature
4. temperaturecooled to about 0° C.
5. stirringstirred for about 1 hr
6. filtrationThe precipitated crystals were collected by filtration
7. washwashed with ethanol (31.2 L)
8. stirringThe obtained wet crystals (about 23 kg) in ethanol (156 L) were stirred at room temperature for about 2 hr
9. temperaturethe mixture was cooled to about 0° C.
10. stirringstirred for about 1 hr
11. filtrationThe precipitated crystals were collected by filtration
12. washwashed with ethanol (31.2 L)
13. additionThe obtained wet crystals (about 20 kg) were added to 1 mol/L aqueous sodium hydroxide solution (104 L)
14. stirringthe mixture was stirred at room temperature for about 1 hr
15. filtrationThe precipitated crystals were collected by filtration
16. washwashed with water (93.6 L)
17. customdried under reduced pressure to a constant amount