反应详情

A mixture of 1-(2-fluoro-phenyl)-3-(piperidin-4-yloxy)-1H-indazole hydrochloride (9.0 g, 0.026 moles) in tetrahydrofuran (20 ml) and water (100 ml) was stirred at room temperature for 0.5 hour as a solution formed. Sodium carbonate (15 g, 0.142 moles) was added portion-wise over a 5-minute period, followed by ether (150 ml). The mixture was shaken and the layers were separated. The aqueous layer was extracted with ether (100 ml). The combined organic layers were dried over magnesium sulfate and concentrated in vacuo to a gum (8.0 g, 99% crude). To this gum was added, all at once, a solution of L-tartaric acid (4.0 g, 0.0267 mol) in water (80 ml). The mixture was stirred for ˜2 minutes when a complete solution formed. Stirring was continued and after ˜2 minutes solid began precipitating. The suspension was stirred at 0° C. for 3 hours and filtered. The solid was rinsed with water (15 ml) and pressed dry under suction. Further drying in vacuo at 50° C. for 16 hours provided 10.2 g (85.5%) of the L-tartrate salt—1-(2-fluoro-phenyl)-3-(piperidin-4-yloxy)-1H-indazole L-tartrate.

1. customformed
2. stirringThe mixture was shaken
3. customthe layers were separated
4. extractionThe aqueous layer was extracted with ether (100 ml)
5. dry with materialThe combined organic layers were dried over magnesium sulfate
6. concentrationconcentrated in vacuo to a gum (8.0 g, 99% crude)
7. additionTo this gum was added
8. stirringThe mixture was stirred for ˜2 minutes when a complete solution
9. customformed
10. stirringStirring
11. waitwas continued and after ˜2 minutes
12. customsolid began precipitating
13. stirringThe suspension was stirred at 0° C. for 3 hours
14. filtrationfiltered
15. washThe solid was rinsed with water (15 ml)
16. custompressed dry under suction
17. customFurther drying in vacuo at 50° C. for 16 hours