Reaction #1483064

Reaction equation

1H-indole-5-carboxylic acid

sodium hydride

iodomethane

DMF

→

1-methyl-1H-indole-5-carboxylic acid methyl ester

Yield 93.0%

Conditions

Workup

1. 1
   OtherThe reaction mixture was then quenched with water (5 mL)
2. 2
   workup.ADDITIONdiluted with ether (150 mL) and ethyl acetate (50 mL)
3. 3
   WashAfter washing with aq. NH4Cl (100 mL), water (100 mL)
4. 4
   Dryingbrine (100 mL), the organic layer was dried over MgSO4
5. 5
   Filtrationfiltered
6. 6
   Concentrationconcentrated

Procedure

A solution of 1H-indole-5-carboxylic acid (1.6 g, 10 mmol), sodium hydride (1.2 g, 30 mmol), iodomethane (6.2 mL, 100 mmol) and DMF (40 mL) was stirred and room temperature for 24 hr. The reaction mixture was then quenched with water (5 mL) and diluted with ether (150 mL) and ethyl acetate (50 mL). After washing with aq. NH4Cl (100 mL), water (100 mL) and then brine (100 mL), the organic layer was dried over MgSO4, filtered and concentrated. The remaining material was subjected to flash chromatography (ethyl acetate/hexane 1:4) to provide 1-methyl-1H-indole-5-carboxylic acid methyl ester as a crystalline solid (1.77 g, 93% yield). 1H NMR (400 MHz, CDCl3) δ 8.40 (s, 1H), 7.94 (d, 1H, J=9.0 Hz), 7.34 (d, 1H, J=9.0 Hz), 7.12 (d, 1H, J=2.9 Hz), 6.60 (d, 1H, J=2.9 Hz), 3.94 (s, 3H), 3.83 (s, 3H).

Source