Dimethylamine → (5-ethoxy-1H-indol-ylmethyl)-dimethyl-amine

HRID 41059

Reaction equation

[CH2:1]([O:3][C:4]1[CH:5]=[C:6]2[C:10](=[CH:11][CH:12]=1)[NH:9][CH:8]=[CH:7]2)[CH3:2].[CH3:13][NH:14][CH3:15].[CH2:16]=O.[OH-].[Na+]>ClCCl.CO.C(O)(=O)C>[CH2:1]([O:3][C:4]1[CH:5]=[C:6]2[C:10](=[CH:11][CH:12]=1)[N:9]([CH2:13][N:14]([CH3:16])[CH3:15])[CH:8]=[CH:7]2)[CH3:2]

Participants

Conditions

Temperature: 0 °C

Procedure

A mixture of 5-ethoxy-indole (7.84 g, 48.7 mmol), 40% aqueous dimethylamine (9.25 ml, 73 mmol, 1.5 equiv), and 96% acetic acid (30 ml) is stirred at 0° C., then 36% aqueous formaldehyde solution (6.33 ml, 82.7 mmol, 1.7 equiv) is added drop wise. The mixture is allowed to come to room temperature, and after stirring overnight TLC (dichloromethane-methanol, 4:1) indicates the absence of starting material. 10% Aqueous NaOH (150 ml) is added and the mixture is stirred at room temperature for 2 h. It is then extracted with dichloromethane (4×200 ml), the organic layer is dried and concentrated. The residue is purified by column chromatography (dichloromethane-methanol, 4:1→methanol-aqueous ammonia 50:1) to give crude product (10.18 g, 96%), which is crystallized from acetone to provide pure (5-ethoxy-1H-indol-ylmethyl)-dimethyl-amine (10.2 g, 96%) as white crystals. M.p. 95-97° C.

Workup

customto come to room temperature
stirringthe mixture is stirred at room temperature for 2 h
extractionIt is then extracted with dichloromethane (4×200 ml)
customthe organic layer is dried
concentrationconcentrated
customThe residue is purified by column chromatography (dichloromethane-methanol, 4:1→methanol-aqueous ammonia 50:1)
customto give crude product (10.18 g, 96%), which
customis crystallized from acetone

Sources & evidence

ORD record: ord-389c3916604348d4a7883e4a21a3270a
Source dataset: uspto-grants-2013_09
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08530493B2

Linked notes

Loading…