反应详情

温度

70 °C

4-(2,6-Dioxo-1,3-dipropyl-2,3,6,7-tetrahydro-1H-purin-8-yl)-bicyclo[2.2.2]octane-1-carbaldehyde (XI, Example 87a, 1 wt) and tetrahydrofuran (16.5 vol) are mixed under nitrogen and methyl(triphenylphosphoranylidene) acetate (1.85 wt) is added. The reaction mixture is heated to 65 to 75° C. and the reaction mixture stirred at this temperature until the starting aldehyde has been consumed as determined by NMR. The mixture is cooled to 35 to 40° C. and a solution of lithium hydroxide (0.45 wt) in water (16.5 vol) is added. The mixture is heated to reflux and the mixture stirred at reflux until the hydrolysis of the ester is complete (as determined by NMR, typical reaction time 3 to 6 hours). The reaction mixture is cooled to 35 to 40° and the organic solvent removed in vacuo at 40 to 45°. Ethyl acetate (10 vol) and water (6 vol) are added to the aqueous residue and the mixture is vigorously stirred for 5 to 15 mins. The phases are separated and the aqueous phase is washed with ethyl acetate (2×10 vol). The aqueous phase is filtered. The filtrate is cooled to 0 to 5° and acidified to pH=1 with concentrated hydrochloric acid (0.90 vol). The mixture is stirred at 0 to 5° for 45 to 75 mins. The resultant slurry is filtered and the filter pad washed with water (1 vol). The solid is dried in vacuo at 45 to 55° for 16 to 24 hours to give the title compound.

1. customhas been consumed
2. temperatureThe mixture is cooled to 35 to 40° C.
3. additiona solution of lithium hydroxide (0.45 wt) in water (16.5 vol) is added
4. temperatureThe mixture is heated
5. temperatureto reflux
6. temperatureat reflux until the hydrolysis of the ester
7. custom(as determined by NMR, typical reaction time 3 to 6 hours)
8. temperatureThe reaction mixture is cooled to 35 to 40°
9. customthe organic solvent removed in vacuo at 40 to 45°
10. additionEthyl acetate (10 vol) and water (6 vol) are added to the aqueous residue
11. stirringthe mixture is vigorously stirred for 5 to 15 mins
12. customThe phases are separated
13. washthe aqueous phase is washed with ethyl acetate (2×10 vol)
14. filtrationThe aqueous phase is filtered
15. temperatureThe filtrate is cooled to 0 to 5°
16. stirringThe mixture is stirred at 0 to 5° for 45 to 75 mins
17. filtrationThe resultant slurry is filtered
18. washthe filter pad washed with water (1 vol)
19. customThe solid is dried in vacuo at 45 to 55° for 16 to 24 hours