Isopropanol → N-(2-(6-Fluoro-1H-indol-3-yl)ethyl)-3-(2,2,3,3-tetrafluoropropyl)benzylamine

HRID 1666879Notes

Reaction equation

HRID 1666879 reaction equation
[F:1][C:2]([F:15])([CH:12]([F:14])[F:13])[CH2:3][C:4]1[CH:11]=[CH:10][CH:9]=[CH:8][C:5]=1C=O.[F:16][C:17]1[CH:18]=[C:19]2[C:26](=[CH:27][CH:28]=1)[C:22]([CH2:23][CH2:24][NH2:25])=[CH:21][NH:20]2.[CH:29](O)(C)C>>[F:16][C:17]1[CH:18]=[C:19]2[C:26]([C:22]([CH2:23][CH2:24][NH:25][CH2:29][C:10]3[CH:9]=[CH:8][CH:5]=[C:4]([CH2:3][C:2]([F:1])([F:15])[CH:12]([F:13])[F:14])[CH:11]=3)=[CH:21][NH:20]2)=[CH:27][CH:28]=1

Participants

4

Reactant 3

HCID 3776IsopropanolHCID 8540242-(6-fluoro-1H-indol-3-yl)ethanamineHCID 210713962,2,3,3-Tetrafluoropropylbenzaldehyde

Product 1

HCID 86612281N-(2-(6-Fluoro-1H-indol-3-yl)ethyl)-3-(2,2,3,3-tetrafluoropropyl)benzylamine

Conditions

Temperature
50 °C

Procedure

Combine isopropanol (500 g), 2,2,3,3-tetrafluoropropylbenzaldehyde (116.8 g), and 6-fluorotryptamine (1.15 equiv.). Heat to reflux over about 1.5 hour. After 30 minutes at the reflux, distill and over 30 minutes collect about 380 g of distillate. Cool the reaction mixture to 50° C. and add NaBH4 (19.71 g) in one portion. After 1 hour at 50° C., slowly add water over 15 minutes and allow the resulting solution to cool to room temperature overnight. Distill the isopropanol under reduced pressure to give a residue and extract with dichloromethane, combine organic layers, and treat with 1N aqueous HCl (650 mL) to give a solid. Stir the heavy suspension for 2 hours at 20-25° C. Collect the solid by filtration, wash with dichloromethane and dry at 50° C. under vacuum overnight to afford title compound.

Workup

  1. temperatureHeat
  2. temperatureto reflux over about 1.5 hour
  3. distillationdistill and over 30 minutes
  4. distillationcollect about 380 g of distillate
  5. additionadd NaBH4 (19.71 g) in one portion
  6. waitAfter 1 hour at 50° C.
  7. waitslowly add water over 15 minutes
  8. temperatureto cool to room temperature overnight
  9. distillationDistill the isopropanol under reduced pressure
  10. customto give a residue
  11. extractionextract with dichloromethane
  12. additiontreat with 1N aqueous HCl (650 mL)
  13. customto give a solid
  14. customCollect the solid
  15. filtrationby filtration
  16. washwash with dichloromethane
  17. customdry at 50° C. under vacuum overnight

Sources & evidence

ORD record
ord-0de6f6259af74ef1b98b49dceb55d7b7
Source dataset
uspto-grants-2011_10
Patent number
US08044090B2

Reaction notes

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