Sodium Hydroxide → 4-{1-[2-(3-Fluoro-phenyl)-ethylamino]-indan-5-yloxy}-benzamide

HRID 422253Notes

Reaction equation

HRID 422253 reaction equation
O=[C:2]1[C:10]2[C:5](=[CH:6][C:7]([O:11][C:12]3[CH:20]=[CH:19][C:15]([C:16]([NH2:18])=[O:17])=[CH:14][CH:13]=3)=[CH:8][CH:9]=2)[CH2:4][CH2:3]1.[F:21][C:22]1[CH:23]=[C:24]([CH:28]=[CH:29][CH:30]=1)[CH2:25][CH2:26][NH2:27].[OH-].[Na+]>CC(O[Ti](OC(C)C)(OC(C)C)OC(C)C)C.Cl[Ti](Cl)(Cl)Cl.C1COCC1>[F:21][C:22]1[CH:23]=[C:24]([CH2:25][CH2:26][NH:27][CH:2]2[C:10]3[C:5](=[CH:6][C:7]([O:11][C:12]4[CH:20]=[CH:19][C:15]([C:16]([NH2:18])=[O:17])=[CH:14][CH:13]=4)=[CH:8][CH:9]=3)[CH2:4][CH2:3]2)[CH:28]=[CH:29][CH:30]=1

Participants

7

Reactant 3

HCID 14798Sodium HydroxideHCID 5339282-(3-Fluorophenyl)ethanamineHCID 597506634-(1-Oxo-indan-5-yloxy)-benzamide2×

Product 1

HCID 597506524-{1-[2-(3-Fluoro-phenyl)-ethylamino]-indan-5-yloxy}-benzamideYield 6%

Reagents, catalysts & solvents 3

HCID 24193Titanium TetrachlorideCatalystHCID 178460666HCID 178460666, compoundCatalystHCID 8028TetrahydrofuranSolvent

Procedure

In a round bottom flask, combine 4-(1-Oxo-indan-5-yloxy)-benzamide (Intermediate 24, 45.0 mg, 0.17 mmol), m-Fluorophenethylamine (33 uL, 0.25 mmol), THF (5 mL), and Ti(OiPr)4 (0.1 mL, 0.27 mmol) at 0° C. under nitrogen atmosphere. Stir the reaction for 3 hours then add TiCl4 (0.3 mL, 0.27 mmol) at 0° C. For the next 2 hours, warm the reaction to room temperature and then add BH3SMe2 (0.09 mL, 0.17 mmol). Stir the reaction at room temperature for 12 hours, then add 1N NaOH (aq) and stir for 2 hours. Centrifuge and decant the reaction into a separatory funnel and wash the organic phase with water and dry over Na2SO4. Concentrate the reaction under reduced pressure and purify using reverse phase chromatography (5% to 95% 0.001% TFA buffer in acetonitrile/water) to afford 3.5 mg, 0.01 mmol (6% yield) of the title compound:

Workup

  1. customIn a round bottom flask, combine
  2. customat 0° C.
  3. customthe reaction for 3 hours
  4. customat 0° C
  5. temperatureFor the next 2 hours, warm
  6. customthe reaction to room temperature
  7. stirringStir
  8. customthe reaction at room temperature for 12 hours
  9. stirringstir for 2 hours
  10. customCentrifuge and decant
  11. customthe reaction into a separatory funnel
  12. washwash the organic phase with water
  13. dry with materialdry over Na2SO4
  14. concentrationConcentrate
  15. customthe reaction under reduced pressure
  16. custompurify

Sources & evidence

ORD record
ord-07bffc67f95544c983657d49ec884165
Source dataset
uspto-grants-2012_01
Patent number
US08101638B2

Reaction notes

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