反应详情

温度

2.5 °C

Lithium aluminum hydride (pellets, 2.90 g, 0.0764 mol) is added to a stirred solution of N-methoxy-N-methyl-5,6-dihydro-4H-pyrrolo[1,2-b]pyrazole-2-carboxamide (30.0 g, 0.154 mol) in anhydrous tetrahydrofuran (300 mL) at 0-5° C. and stirred overnight (20 hours) at 0-5° C. under nitrogen. The mixture is then slowly added to a flask containing water (50 ml) and tetrahydrofuran (50 ml) maintained at 5-15° C. Anhydrous sodium sulfate (8.0 g) and anhydrous magnesium sulfate (4.0 g) are added and the mixture is stirred for 0.5 hours. The mixture is filtered, and the filter pad is washed with tetrahydrofuran (100 ml). The filtrate and washings are evaporated under diminished pressure and the residue is stirred for 20 minutes with dichloromethane (150 ml) and 1.5 N hydrochloric acid (40 ml). The phases are separated and water (200 ml) containing dissolved sodium hydrogensulfite (22 g) is added to the organic phase. The mixture is stirred for 20 minutes and the phases are separated. Fresh dichloromethane (150 mL) and 10 N sodium hydroxide (22 mL) are added (with cooling) to the aqueous phase. The mixture is stirred for 20 minutes and the phases are separated. The organic phase is washed with water (100 ml). The dichloromethane extract is evaporated at 20-70° C. to give an oil which crystallizes on cooling to provide 16.1 g (77%) of 5,6-dihydro-4H-pyrrolo-[1,2-b]-pyrazole-2-carbaldehyde as a light yellow, crystalline solid having HPLC-MS purity 99.95% (HPLC conditions as in example 15).

1. additionThe mixture is then slowly added to a flask
2. temperaturemaintained at 5-15° C
3. stirringthe mixture is stirred for 0.5 hours
4. filtrationThe mixture is filtered
5. washthe filter pad is washed with tetrahydrofuran (100 ml)
6. customThe filtrate and washings are evaporated under diminished pressure
7. stirringthe residue is stirred for 20 minutes with dichloromethane (150 ml) and 1.5 N hydrochloric acid (40 ml)
8. customThe phases are separated
9. additionwater (200 ml) containing
10. dissolutiondissolved sodium hydrogensulfite (22 g)
11. additionis added to the organic phase
12. stirringThe mixture is stirred for 20 minutes
13. customthe phases are separated
14. additionFresh dichloromethane (150 mL) and 10 N sodium hydroxide (22 mL) are added
15. temperature(with cooling) to the aqueous phase
16. stirringThe mixture is stirred for 20 minutes
17. customthe phases are separated
18. washThe organic phase is washed with water (100 ml)
19. extractionThe dichloromethane extract
20. customis evaporated at 20-70° C.
21. customto give an oil which
22. customcrystallizes
23. temperatureon cooling