Diethyl Ether → L-tartrate salt-1-(2-fluoro-phenyl)-3-(piperidin-4-yloxy)-1H-indazole L-tartrate

HRID 30415

Reaction equation

HRID 30415 reaction equation
Cl.[F:2][C:3]1[CH:8]=[CH:7][CH:6]=[CH:5][C:4]=1[N:9]1[C:17]2[C:12](=[CH:13][CH:14]=[CH:15][CH:16]=2)[C:11]([O:18][CH:19]2[CH2:24][CH2:23][NH:22][CH2:21][CH2:20]2)=[N:10]1.C(=O)([O-])[O-].[Na+].[Na+].CCOCC.[C:36]([OH:45])(=[O:44])[C@@H:37]([C@H:39]([C:41]([OH:43])=[O:42])[OH:40])[OH:38]>O1CCCC1.O>[C:41]([C@@H:39]([C@H:37]([C:36]([OH:45])=[O:44])[OH:38])[OH:40])([OH:43])=[O:42].[F:2][C:3]1[CH:8]=[CH:7][CH:6]=[CH:5][C:4]=1[N:9]1[C:17]2[C:12](=[CH:13][CH:14]=[CH:15][CH:16]=2)[C:11]([O:18][CH:19]2[CH2:24][CH2:23][NH:22][CH2:21][CH2:20]2)=[N:10]1.[C:41]([C@@H:39]([C@H:37]([C:36]([OH:45])=[O:44])[OH:38])[OH:40])([OH:43])=[O:42]

Participants

7

Reactant 4

HCID 3283Diethyl EtherHCID 10340Sodium CarbonateHCID 444305L-Tartaric acidHCID 574205491-(2-Fluoro-phenyl)-3-(piperidin-4-yloxy)-1h-indazole hydrochloride

Product 1

HCID 131727052L-tartrate salt-1-(2-fluoro-phenyl)-3-(piperidin-4-yloxy)-1H-indazole L-tartrateYield 124.9%

Reagents, catalysts & solvents 2

HCID 962WaterSolvent2×HCID 8028TetrahydrofuranSolvent

Procedure

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.

Workup

  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

Sources & evidence

ORD record
ord-ec8a8af7f4054d599a8a1236ba950fd0
Source dataset
uspto-grants-2008_09
Patent number
US07423054B2

Linked notes

Loading…