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

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Reaction Conditions

Reaction Steps

Method B A solution of 3-chloropropanol (142.47 g, 1.51 mole) in dichloromethane (1200 ml) was cooled to -20° C. In a second vessel dichloromethane (1300 ml), methyl indole-3-carboxylate (240.0 g, 1.37 mole) and 1,4-diazabicyclo[2.2.2]octane (84.52 g 0.75 mole) 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 sulphonic 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 (2500 ml) was added and stirred. The organic layer was separated and washed twice with 10% sodium carbonate solution (2500 ml each wash). The organic layer was dried over anhydrous sodium sulfate, filtered and concentrated under reduced pressure. The concentrate was triturated with ethyl acetate (120 ml) and the mixture stirred at 0° C. for about 1 hour. The resulting solid was filtered, washed a small quantity of ethyl acetate and dried under vacuum to give methyl 2-(3-chloropropoxy)-indole-3-carboxylate (202.5 g) as a white crystalline solid in 55% yield.

Provenance & Evidence