Sodium t-butoxide → 1,1-Dimethylethyl 6-bromo-1-methyl-1H-indole-3-carboxylate

Participants

Reaction Conditions

Reaction Steps

Dissolve 6-bromo-1-methyl-1H-indole-3-carboxylic acid methyl ester (17.16 Kg, 63.98 mol) in toluene (134.5 Kg) under nitrogen atmosphere. Stir at least 15 minutes. Add magnesium sulfate to dry and charcoal to de-colorize the solution and stir at least 30 minutes. Filter the mixture. Dissolve sodium tert-butoxide (21.5 Kg, 223.70 mol) in toluene (43.7 kg) under a nitrogen atmosphere. Add the starting material solution mixture to the sodium tert-butoxide solution and heat the reaction mixture slowly over approximately 2-3 hours to a temperature of 105-108° C. and maintain temperature for 30-60 minutes. Follow by TLC until no starting material is observed. Cool the reaction to room temperature and quench the mixture into water (177.2 Kg) cooled to 0-10° C. Stir the reaction mixture for at least 30 minutes and separate the aqueous layer and emulsion. Wash the organic mixture with brine (2×47.7 Kg) maintaining the emulsion with the aqueous brine wash. Extract the combined aqueous layer with toluene (2×29.9 Kg). Filter organic layer and any emulsion through diatomaceous earth. Wash the filter cake with toluene (6.1 Kg). Wash the combined organic layers with brine (2×47.7 Kg). Add magnesium sulfate (7 Kg) and charcoal (850 g) and stir for 30 minutes. Filter the mixture and concentrate the filtrate at 50-55° C. to the lowest stirrable volume. Discontinue heating and add heptane (47.3 Kg) to the mixture. Cool the suspension to 0-5° C. for at least 2 hours and collect the solids by filtration. Rinse the solids with heptane cooled to 0-5° C. Dry solids at 30-35° C. for 12-72 hours under vacuum to give 13.110 Kg (66%) of the title compound.

Provenance & Evidence