反应详情

4-(2,6-Dioxo-1,3-dipropyl-2,3,6,7-tetrahydro-1H-purin-8-yl)-bicyclo[2.2.22]octane-1-carbaldehyde (XI, Example 97b, 0.300 kg) and tetrahydrofuran (4.95 l) are mixed under an atmosphere of nitrogen and methyl(triphenylphosphoranylidene) acetate (0.555 kg) is added. The reaction mixture is heated to 65 to 750 and the reaction mixture stirred at this temperature until the starting aldehyde is consumed (17 hours). The mixture is cooled to 35 to 40° and a mixture of sodium hydroxide (0.132 kg) in water (4.95 l) is added. The mixture is heated to reflux and stirred until the hydrolysis of the ester is complete (3 hours). The reaction mixture is cooled to 35 to 400 and the organic solvent removed in vacuo at 40 to 45°. Ethyl acetate (3.00 l) and water (1.80 l) are added to the aqueous residue and the mixture is vigorously stirred for 15 mins. The layers are separated and the aqueous layer is washed with ethyl acetate (2×3.00 l). The aqueous layer is filtered, the filtrate is cooled to 0 to 50 and acidified to pH=1 with concentrated hydrochloric acid (0.270 l). The mixture is stirred at 0 to 50 for 1 hour. The resultant slurry is filtered and the filter pad washed with water (0.300 l). The solid is dried in vacuo at 45 to 550 for 24 hours to the title compound.

1. temperatureThe reaction mixture is heated to 65 to 750
2. customis consumed (17 hours)
3. temperatureThe mixture is cooled to 35 to 40°
4. additiona mixture of sodium hydroxide (0.132 kg) in water (4.95 l)
5. additionis added
6. temperatureThe mixture is heated
7. temperatureto reflux
8. custom(3 hours)
9. temperatureThe reaction mixture is cooled to 35 to 400
10. customthe organic solvent removed in vacuo at 40 to 45°
11. additionEthyl acetate (3.00 l) and water (1.80 l) are added to the aqueous residue
12. stirringthe mixture is vigorously stirred for 15 mins
13. customThe layers are separated
14. washthe aqueous layer is washed with ethyl acetate (2×3.00 l)
15. filtrationThe aqueous layer is filtered
16. temperaturethe filtrate is cooled to 0 to 50
17. stirringThe mixture is stirred at 0 to 50 for 1 hour
18. filtrationThe resultant slurry is filtered
19. washthe filter pad washed with water (0.300 l)
20. dry with materialThe solid is dried in vacuo at 45 to 550 for 24 hours to the title compound