Formaldehyde → 4-Benzyloxy-1-hydroxymethylindole

HRID 490819Notes

Reaction equation

HRID 490819 reaction equation
[OH:1][CH2:2][N:3]1[C:11]2[C:6](=[C:7]([OH:12])[CH:8]=[CH:9][CH:10]=2)[CH:5]=[CH:4]1.[CH2:13](OC1C=CC=C2C=1C=CN2)[C:14]1[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=1.C=O.[OH-].[Na+]>CCO>[CH2:13]([O:12][C:7]1[CH:8]=[CH:9][CH:10]=[C:11]2[C:6]=1[CH:5]=[CH:4][N:3]2[CH2:2][OH:1])[C:14]1[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=1

Participants

6

Reactant 4

HCID 712FormaldehydeHCID 14798Sodium HydroxideHCID 884654-(phenylmethoxy)-1H-indoleHCID 247769031-(Hydroxymethyl)-1H-indol-4-ol

Product 1

HCID 247769004-Benzyloxy-1-hydroxymethylindole

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Procedure

1-Hydroxymethyl-4-hydroxy-indole: A solution of 4-benzyloxyindole (1.0 g, 4.48 mmol), formaldehyde (2.0 mL, 26.8 mmol) and 2 N NaOH (2.24 mL, 4.48 mmol) in 10 mL EtOH was stirred at the room temperature for 4 h. The solvent was removed in vacuo. The crude material was purified by flash column chromatography (3:1, hexane:ethyl acetate) to yield 1.13 g of 4-benzyloxy-1-hydroxymethylindole, which was hydrogenated by 5% Pd/C in 40 mL methanol under H2 (50 psi) to yield 580 mg (79.5%) of the title compound. 1H NMR (CDCl3): 7.15-7.07 (m, 3H), 6.60-6.55 (m, 2H), 5.62 (d, J=7.5 Hz, 2H), 4.93 (s, 1H), 2.37 (t, J=7.2 Hz, 1H).

Workup

  1. customThe solvent was removed in vacuo
  2. customThe crude material was purified by flash column chromatography (3:1, hexane:ethyl acetate)

Sources & evidence

ORD record
ord-eda25917d1d44cd0b5ed823df29920f5
Source dataset
uspto-grants-2009_05
Patent number
US07528164B2

Reaction notes

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