Sodium Hydroxide → 2-(6-fluoro-1H-indol-3-yl)ethanamine

HRID 1371950Notes

Reaction equation

HRID 1371950 reaction equation
[F:1][C:2]1[CH:10]=[C:9]2[C:5]([C:6]([CH2:11][C:12]#[N:13])=[CH:7][NH:8]2)=[CH:4][CH:3]=1.[OH-].[Na+]>C1COCC1>[F:1][C:2]1[CH:10]=[C:9]2[C:5](=[CH:4][CH:3]=1)[C:6]([CH2:11][CH2:12][NH2:13])=[CH:7][NH:8]2

Participants

4

Reactant 2

HCID 14798Sodium HydroxideHCID 21071427(6-Fluoro-1H-indol-3-yl)acetonitrile

Product 1

HCID 8540242-(6-fluoro-1H-indol-3-yl)ethanamine

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

Combine 2-(6-fluoro-1H-indol-3-yl)acetonitrile (165 g, 0.925 mol) and THF (1.32 L). Slowly add 1M solution of BH3 (2.042 L, 1,832 Kg, 0.131 mol) in THF over about 40 minutes. When the addition is complete, heat to reflux within 1 hour. After 1 hour at reflux, cool to room temperature and the reaction mixture, over about 25 minutes, to a well-stirred 15% aqueous solution of NaOH (1.9 L, 9.5 mol). After addition, slowly and gradually heat to 50° C. After 1 hour, heat 60° C. After 30 minutes, heat to reflux for 1 hour. Cool to room temperature and stir overnight, decant the alkaline aqueous layer and replace by water. Heat to 30° C. under a pressure of 200 mbars in order to distill the THF until about 2.5 kg of distilate is removed. Extract the mixture with dichloromethane. Slowly add to the combined organic layers over a 25 minutes a mixture of 37% aqueous HCl (143 g) and water (220 g) and stir to give a solid. After 1 hour, collect the solid by filtration, wash with of dichloromethane, and dry overnight to afford of the hydrochloride salt of the title compound.

Workup

  1. additionWhen the addition
  2. temperatureheat
  3. temperatureto reflux within 1 hour
  4. temperatureAfter 1 hour at reflux
  5. additionAfter addition
  6. temperatureslowly and gradually heat to 50° C
  7. waitAfter 1 hour
  8. temperatureheat 60° C
  9. waitAfter 30 minutes
  10. temperatureheat
  11. temperatureto reflux for 1 hour
  12. temperatureCool to room temperature
  13. customdecant the alkaline aqueous layer
  14. temperatureHeat to 30° C. under a pressure of 200 mbars in order
  15. distillationto distill the THF until about 2.5 kg of distilate
  16. customis removed
  17. extractionExtract the mixture with dichloromethane
  18. additionSlowly add to the combined organic layers over a 25 minutes
  19. additiona mixture of 37% aqueous HCl (143 g) and water (220 g)
  20. stirringstir
  21. customto give a solid
  22. waitAfter 1 hour
  23. customcollect the solid
  24. filtrationby filtration
  25. washwash with of dichloromethane
  26. customdry overnight

Sources & evidence

ORD record
ord-171eb216b41f4e5c8e48c34bb385b5f0
Source dataset
uspto-grants-2007_01
Patent number
US07157488B2

Reaction notes

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