Methanesulfonic Acid → Methyl 2-(3-chloropropoxy)indole-3-carboxylate

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Reaction Conditions

Reaction Steps

Method C A solution of 3-chloropropanol (142.47 g, 1.51 mol) in dichloromethane (1200ml) was cooled to -20° C. In a second vessel dichloromethane (1300 ml), methyl indole-3-carboxylate (240.0 g, 1.37 mol) and 1,4-diazabicyclo[2.2.2]octane (84.52 g 0.75 mol) were cooled to 0° C. N-Chlorosuccinimide (201.22 g 1.51 mole) was added to the second vessel and stirred at 0° C. for 10 minutes. In the meantime methane sulfonic acid (10.56 ml) was added to the first vessel. The solution in the second vessel was added to the first vessel keeping the temperature below about 0° C., and the resulting mixture stirred for a further 2.5 hours at -5 to 0° C. 10% Sodium carbonate solution (1250 ml) was added and the mixture stirred for about 30 minutes. The organic layer was separated and washed once more with 10% sodium carbonate solution (1250 ml) and once with water (1250 ml). The organic layer was dried over anhydrous sodium sulfate, filtered and concentrated under reduced pressure. The concentrate was triturated with toluene (400 ml) and the mixture stirred at 0° C. for about 1 hour. The resulting solid was filtered, washed with toluene and dried in vacuo to give methyl 2-(3-chloropropoxy)-indole-3-carboxylate (245.5 g) as a white crystalline solid in 67% yield.

Provenance & Evidence