Hydrochloric Acid → 1-(3-Aminopropyl)-4-(2-methoxyphenyl)piperazine

Participants

Reaction Conditions

Reaction Steps

3-[4-(2-Methoxyphenyl)piperazin-1-yl]propionamide (3 g, 11.4 mmol) was suspended in 30 mL of freshly distilled THF and borane-tetrahydrofuran complex (17.5 mL, 1M in THF, 17.5 mmol) was added at a rate such that the reaction temperature remained below 26° C. The mixture was stirred at gentle reflux (67° C.) for 6.5 hours, with additional borane-tetrahydrofuran complex (6 mL, 4 mL and 4 mL) added after 1, 3.5 and 5 hours, respectively. The mixture was cooled to 22° C. and then hydrochloric acid (20 mL, 6N, 120 mmol) was added at a rate such that the reaction temperature did not exceed 35° C. The mixture was heated at reflux for 20 minutes and cooled to room temperature and then 50% sodium hydroxide was added at a rate such that the reaction temperature did not exceed 60° C. The aqueous layer was separated and extracted with THF (2×25 mL). The combined organic layers were dried (K2CO3) and filtered. The filtrate was concentrated under reduced pressure to give 3-[4-(2-methoxyphenyl)-piperazin-1-yl]propylamine (2.5 g, 10 mmol) as an oil.

Provenance & Evidence