Aluminium lithium hydride → 1H-Indole-3-ethanamine, 4-methoxy-

HRID 1666814Notes

Reaction equation

HRID 1666814 reaction equation
[H-].[H-].[H-].[H-].[Li+].[Al+3].[N+:7]([CH:10]=[CH:11][C:12]1[C:20]2[C:15](=[CH:16][CH:17]=[CH:18][C:19]=2[O:21][CH3:22])[NH:14][CH:13]=1)([O-])=O>C1COCC1>[CH3:22][O:21][C:19]1[CH:18]=[CH:17][CH:16]=[C:15]2[C:20]=1[C:12]([CH2:11][CH2:10][NH2:7])=[CH:13][NH:14]2

Participants

4

Reactant 2

HCID 21226445Aluminium lithium hydride2×HCID 67443432HCID 67443432, compound

Product 1

HCID 192191H-Indole-3-ethanamine, 4-methoxy-

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

Combine LiAlH4 (6.78 g; 178.74 mmol; 6 eq) and anhydrous THF. Dissolve 3-(2-nitrovinyl)-4-methoxy-1H-indole (6.5 g; 29.79 mmol) in anhydrous THF and add dropwise to the LiAlH4 solution with vigorous stirring. After the addition is complete, heat to reflux. After 1 hour cool to ambient temperature and stir. After 16 hours, quench the excess LiAlH4 as described in J. Med. Chem. 1995, 38, 2050. Filter the gray suspension through celite and rinse the celite with ethyl acetate. Evaporate the filtrate in vacuo to residue. Chromatograph the residue on silica gel eluting with 1 L of CHCl3MeOH/NH4OH (95:10:1) and then 1 L of CHCl3/MeOH/NH4OH (90:10:1) as the mobile phase. Pool fractions containing the product and evaporate to give the title compound as a tan solid: 1H NMR (300 MHz, d6-DMSO): 2.96 (t, 2H); 3.42 (t, 2H); 3.83 (s, 3H); 6.42 (dd, 1H); 6.93 (m, 3H); 10.7 (s, 1H); MS (ES+): m/z 191 (M+H)+; 174 (M−NH2)+; 159 (M−OCH3)+; (ES−): m/z 189 (M−H)−.

Workup

  1. additionAfter the addition
  2. temperatureheat to reflux
  3. customquench the excess LiAlH4
  4. filtrationFilter the gray suspension through celite
  5. washrinse the celite with ethyl acetate
  6. customEvaporate the filtrate in vacuo to residue
  7. additionPool fractions containing the product
  8. customevaporate

Sources & evidence

ORD record
ord-39b9d6391b2340f5878285ae72796847
Source dataset
uspto-grants-2011_10
Patent number
US08044090B2

Reaction notes

Loading…