Diisopropylethylamine → 2-(6-Fluoro-1H-indol-3-yl)ethyl-3-(2,2,2-trifluoroethoxy)benzylamine

HRID 1666838Notes

Reaction equation

HRID 1666838 reaction equation
C(O)(=O)C(O)=O.[F:7][C:8]1[CH:9]=[C:10]2[C:17](=[CH:18][CH:19]=1)[C:13]([CH2:14][CH2:15][NH2:16])=[CH:12][NH:11]2.C(N(CC)C(C)C)(C)C.[F:29][C:30]([F:42])([F:41])[CH2:31][O:32][C:33]1[CH:34]=[C:35]([CH:38]=[CH:39][CH:40]=1)[CH:36]=O.[BH4-].[Na+]>CCO>[F:7][C:8]1[CH:9]=[C:10]2[C:17]([C:13]([CH2:14][CH2:15][NH:16][CH2:36][C:35]3[CH:38]=[CH:39][CH:40]=[C:33]([O:32][CH2:31][C:30]([F:29])([F:41])[F:42])[CH:34]=3)=[CH:12][NH:11]2)=[CH:18][CH:19]=1

Participants

6

Reactant 4

HCID 81531DiisopropylethylamineHCID 4311764Sodium borohydrideHCID 47709473-(2,2,2-Trifluoroethoxy)benzaldehydeHCID 210716066-Fluorotryptamine oxalate

Product 1

HCID 587791222-(6-Fluoro-1H-indol-3-yl)ethyl-3-(2,2,2-trifluoroethoxy)benzylamine

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Procedure

Combine 6-fluorotryptamine oxalate (350 mg, 1.3 mmol), N,N-diisopropylethylamine (506 mg, 3.9 mmol), 3-(2,2,2-trifluoroethoxy)benzaldehyde (266 mg, 1.3 mmol), and 4 Å molecular sieves (4 g) in EtOH (30 mL) and reflux for 7 hours. Decant the liquid into a separate flask and treat with NaBH4 (148 mg, 3.9 mmol). Stir 1 hour, concentrate the mixture in vacuo to give a residue. Partition the residue between 25 mL 5 N NaOH and 25 mL dichloromethane. Extract the aqueous layer with 25 mL dichloromethane, combine the organic layers, dry over MgSO4, and concentrate to approximately a 20 mL volume. Chromatograph on silica gel eluting with 1% MeOH in CHCl3 mixed with conc. NH4OH to give the title compound. Combine an EtOAc solution of the title compound with an EtOAc solution of one equivalent of oxalic acid to give a solid, filter, and dry under vacuum to give the oxalate salt of the title compound: ISMS 367 (M+1); Analysis for C9H19ClF4N2O: calcd: C, 55.27; H, 4.42; N, 6.14. found: C, 55.17; H, 4.38; N, 6.09.

Workup

  1. customDecant the liquid into a separate flask
  2. concentrationconcentrate the mixture in vacuo
  3. customto give a residue
  4. customPartition the residue between 25 mL 5 N NaOH and 25 mL dichloromethane
  5. extractionExtract the aqueous layer with 25 mL dichloromethane
  6. dry with materialdry over MgSO4
  7. concentrationconcentrate to approximately a 20 mL volume
  8. additionChromatograph on silica gel eluting with 1% MeOH in CHCl3 mixed with conc. NH4OH

Sources & evidence

ORD record
ord-60f732f569e940098201b1d3c3ca3549
Source dataset
uspto-grants-2011_10
Patent number
US08044090B2

Reaction notes

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