(1,2-DiMethyl-1H-indol-3-yl)-acetic acid synthesis

Yield:2597-28-6 61%

Reaction Conditions:

Stage #1: 2-methyl-3-indoleacetic acidwith sodium hydride in tetrahydrofuran;mineral oil at 0; for 0.5 h;
Stage #2: methyl iodide in tetrahydrofuran;mineral oil at 0 - 20;

Steps:

89.1 SteStep 1: 2-(1,2-dimethyl-1 H-indol-3-yl)acetic acid

A stirring solution of 2-(2-methyl-1 H-indol-3-yl)acetic acid (252.6 mg, 1.3 mmol, example 67, step 2) in dry THF (15 mL) cooled at 0 °C, was added of sodium hydride (158.5 mg, 4.0 mmol, 60% dispersion in mineral oil), and left stirring for about 30 minutes.
After iodomethane (275 μl; 4:4 mmol) was added, the mixture was allowed to warm to room temperature and left stirring overnight.
The reaction was quenched with MeOH at 0 °C, diuted with water and extracted with Et₂O.
The acqueous phase was acidified to pH 1-2 and extracted three times with DCM.
The reunited organic phase was dried over MgSO₄, filtered and concentrated to give the crude product, which was purified by column chromatography (40% EtOAc in PE). Yield: 166.4 mg (61%)

References:

EP3305781,2018,A1 Location in patent:Paragraph 0893; 0894