반응 #68658

반응 방정식

polyethylene

hydrazine

4-methylbenzenesulfonic acid hydrate

di(1H-imidazol-1-yl)methanone

N-Boc glycine

1-(6-chloropyridazin-3-yl)hydrazine

→

tert-butyl (6-chloro-[1,2,4]triazolo[4,3-b]pyridazin-3-yl)methylcarbamate

수율 78.5%

용매

acetonitrile

acetonitrile

acetonitrile

반응 조건

후처리

1. 1
   기타A 2-L round bottom flask flask equipped with a magnetic stirbar
2. 2
   온도The stirred slurry was cooled
3. 3
   기타3-neck, round bottom flask equipped with a mechanical overhead stirrer and a thermocouple w/adapter
4. 4
   온도cooled to <5 deg C
5. 5
   기타The ice bath was removed
6. 6
   온도to warm
7. 7
   기타The flask was then equipped with a heating mantle and a reflux condenser
8. 8
   온도was heated
9. 9
   온도to reflux (82 deg C.) for 13 h
10. 10
    온도cooled back to about 60 deg C
11. 11
    여과filtered through paper
12. 12
    농축The brown filtrate was then concentrated by rotary evaporation
13. 13
    workup.STIRRINGThe resulting thick yellow-brown slurry was stirred in an ice bath
14. 14
    workup.ADDITIONdiluted with ACN (about 100 mL)
15. 15
    workup.STIRRINGAfter stirring for 1 h
16. 16
    기타the solids were isolated by vacuum filtration
17. 17
    세척washed with ice-cold 1:1 ACN/H2O (2×150 mL)
18. 18
    기타air-dried on the
19. 19
    여과filter until
20. 20
    기타was obtained (159 g, 78.5% yield)

실험 절차

A 2-L round bottom flask flask equipped with a magnetic stirbar was charged with di(1H-imidazol-1-yl)methanone (121 g, 749 mmol) and acetonitrile (500 mL). The stirred slurry was cooled by immersing the flask in an ice bath. A solution of N-Boc glycine (125 g, 714 mmol) in acetonitrile (500 mL) was added via a 500-mL addition funnel over the course of 30-45 min. The mixture was aged for 1 h while a 5-L, 3-neck, round bottom flask equipped with a mechanical overhead stirrer and a thermocouple w/adapter was charged with 1-(6-chloropyridazin-3-yl)hydrazine (108 g, 749 mmol) and acetonitrile (900 mL) and cooled to <5 deg C. in an ice bath. The cold solution of the acylimidazole was then transferred via a polyethylene cannula into the thick suspension of the hydrazine over a period of 30-45 min). The ice bath was removed, and the mixture was allowed to warm. After 2.5 h of stirring, 4-methylbenzenesulfonic acid hydrate (143 g, 749 mmol) was added. The flask was then equipped with a heating mantle and a reflux condenser and was heated to reflux (82 deg C.) for 13 h, then cooled back to about 60 deg C. At this point, the warm solution was vacuum filtered through paper. The brown filtrate was then concentrated by rotary evaporation. The resulting thick yellow-brown slurry was stirred in an ice bath and diluted with ACN (about 100 mL). After stirring for 1 h, the solids were isolated by vacuum filtration, washed with ice-cold 1:1 ACN/H2O (2×150 mL) and air-dried on the filter until a freely flowing solid was obtained (159 g, 78.5% yield).

출처