反応 #614978

反応方程式

trimethylsilyl trifluoromethanesulfonate

N,O-bis(trimethylsilyl)acetamide

2-fluoro-1H-purin-6-amine

tetrahydropyranyl acetate

→

title compound

2-Fluoro-9-(tetrahydro-2H-pyran-2-yl)-9H-purin-6-amine

溶媒

acetonitrile

acetonitrile

反応条件

後処理

1. 1
   温度the resulting mixture heated
2. 2
   温度to reflux
3. 3
   温度maintained at that temperature for 2 hours
4. 4
   その他was re-adjusted to 10° C.
5. 5
   温度maintained for a further 1 hour
6. 6
   その他The mixture was then quenched by addition of 1M sodium carbonate (4 L)
7. 7
   workup.ADDITIONAdditional water was added to the suspension (10
8. 8
   その他separated with the aqueous layer
9. 9
   workup.ADDITIONcontaining significant solid inorganics
10. 10
    その他The majority of the aqueous and inorganic solid was separated
11. 11
    温度The organic layer still contained significant solid and was cooled to 0° C.
12. 12
    workup.STIRRINGwith stirring
13. 13
    その他precipitation
14. 14
    ろ過collected by filtration
15. 15
    洗浄the pad was washed very well with water
16. 16
    その他then dried in vacuo at 40° C. overnight

実験手順

N,O-bis(trimethylsilyl)acetamide (975 mL, 3.988 mol) was added to a stirred suspension of 2-fluoro-1H-purin-6-amine (200 g, 1.306 mmol) (available from, for example, AlliedSignal, US) in anhydrous acetonitrile (4 L) in a 10 L controlled lab reactor and the resulting mixture heated to reflux and maintained at that temperature for 2 hours. The circulator was then re-programmed and the reaction mixture cooled to 0° C. A solution of tetrahydropyranyl acetate (preparation described in Tetrahedron Letters 2006, 47(27), 4741) (282 g, 1.959 mol) in anhydrous acetonitrile (500 ml) was then added slowly via a dropping funnel followed by trimethylsilyl trifluoromethanesulfonate (283 mL, 1.567 mol) dropwise via a dropping funnel. No significant exotherm was observed. The circulator temperature was re-adjusted to 10° C. and stirring maintained for a further 1 hour. The mixture was then quenched by addition of 1M sodium carbonate (4 L). A solid precipitate was observed and the pH checked to be basic. Additional water was added to the suspension (10 and on standing the layers separated with the aqueous layer containing significant solid inorganics. The majority of the aqueous and inorganic solid was separated. The organic layer still contained significant solid and was cooled to 0° C. with stirring to encourage further precipitation. The solid was the collected by filtration and the pad was washed very well with water then dried in vacuo at 40° C. overnight to give the title compound as a cream coloured solid (152.8 g).

出典