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

Temperature

67 °C

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.

1. additionwas added at a rate such that the reaction temperature
2. customremained below 26° C
3. additionwith additional borane-tetrahydrofuran complex (6 mL, 4 mL and 4 mL) added after 1, 3.5 and 5 hours
4. temperatureThe mixture was cooled to 22° C.
5. customdid not exceed 35° C
6. temperatureThe mixture was heated
7. temperatureat reflux for 20 minutes
8. temperaturecooled to room temperature
9. customdid not exceed 60° C
10. customThe aqueous layer was separated
11. extractionextracted with THF (2×25 mL)
12. dry with materialThe combined organic layers were dried (K2CO3)
13. filtrationfiltered
14. concentrationThe filtrate was concentrated under reduced pressure

ORD record

ord-578435f0c5c34f929ce1e99c7532a6e5

Source dataset

uspto-grants-1997_11

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US05688795