5-Methoxytryptamine → N-(2-(5-Methoxy-1H-indol-3-yl)-ethyl)-(3-(3,3,3-trifluoropropoxy)benzyl)amine

HRID 1666887Notes

Reaction equation

HRID 1666887 reaction equation
[CH3:1][O:2][C:3]1[CH:14]=[C:13]2[C:6]([NH:7][CH:8]=[C:9]2[CH2:10][CH2:11][NH2:12])=[CH:5][CH:4]=1.[F:15][C:16]([F:29])([F:28])[CH2:17][CH2:18][O:19][C:20]1[CH:21]=[C:22]([CH:25]=[CH:26][CH:27]=1)[CH:23]=O.[BH4-].[Na+]>CCO>[CH3:1][O:2][C:3]1[CH:14]=[C:13]2[C:6](=[CH:5][CH:4]=1)[NH:7][CH:8]=[C:9]2[CH2:10][CH2:11][NH:12][CH2:23][C:22]1[CH:25]=[CH:26][CH:27]=[C:20]([O:19][CH2:18][CH2:17][C:16]([F:15])([F:29])[F:28])[CH:21]=1

Participants

5

Reactant 3

HCID 18335-MethoxytryptamineHCID 4311764Sodium borohydrideHCID 210715093-(3,3,3-Trifluoropropoxy)benzaldehyde

Product 1

HCID 21071636N-(2-(5-Methoxy-1H-indol-3-yl)-ethyl)-(3-(3,3,3-trifluoropropoxy)benzyl)amine

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Procedure

Combine 350 mg (1.8 mmol) 5-methoxytryptamine, 401 mg 3-trifluoropropoxybenzaldehyde (1.8 mmol) and 4 g 4A molecular sieves in 35 mL EtOH and reflux overnight. Decant the liquid into a separate flask and treat with 209 mg (5.5 mmol) NaBH4. Stir the reaction at ambient temperature for 1 hour. Concentrate under vacuum, and partition between 50 mL 1 N NaOH and 25 mL dichloromethane. Extract the aqueous layer with 25 ml dichloromethane and combine the organic layers and concentrate to dryness. Purify the resulting oil by radial chromatography (SiO2; 1% MeOH in CHCl3 mixed with conc. NH4OH) to afford 705 mg (1.8 mmol; 100%) of the desired compound as an oil. Conversion to it's HCl salt by stirring a solution of the compound in 50 mL 50/50 THF/EtOH with 1 g polyvinyl pyridine hydrochloride overnight, filtering and concentrating to a solid. Recrystallize the product from EtOAc: Analysis for C21H23F3N2O2.HCl: calcd: C, 58.81; H, 5.64; N, 6.53. found: C, 58.42; H, 5.44; N, 6.51. ISMS 393 (M+1).

Workup

  1. customDecant the liquid into a separate flask
  2. customthe reaction at ambient temperature for 1 hour
  3. concentrationConcentrate under vacuum
  4. custompartition between 50 mL 1 N NaOH and 25 mL dichloromethane
  5. extractionExtract the aqueous layer with 25 ml dichloromethane
  6. concentrationconcentrate to dryness
  7. customPurify the resulting oil
  8. additionby radial chromatography (SiO2; 1% MeOH in CHCl3 mixed with conc. NH4OH)

Sources & evidence

ORD record
ord-4db00d30774547c3be65780a2d8bc3b3
Source dataset
uspto-grants-2011_10
Patent number
US08044090B2

Reaction notes

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