Triethylamine → 8-(4-Benzyl-piperazin-1-yl)-6-bromo-quinoline

The free base of bis(2-chloroethyl)-benzlyamine (5.12 g, 19.3 mmol) was prepared by washing the HCl salt with 1 M NaOH (200 mL) and extracting into EtOAc. The resulting organic phases were dried over NASO4 and concentrated. To this flask was added 6-bromo-8-amino-quinoline (2.15 g, 9.6 mmol), n-BuOH (100 mL), and Et3N (4 mL, 28.9 mmol). The resulting reaction mixture was stirred at 100° C. overnight. TLC analysis showed starting amine was still present, therefore an additional portion of bis(2-chloroethyl)-benzylamine hydrochloride (5 g) was added. The reaction was heated an additional 72 hours. The cooled reaction mixture was quenched with 1 M NaOH (200 mL) and extracted into EtOAc (3×200 mL). The organic fractions were combined, dried over Na2SO4, and concentrated. The resulting gold oil was purified three times by column chromatography (40% EtOAc/hexanes) affording 1.2 g (33%) of a viscous orange oil which solidified upon standing: mp 65-68° C., MS (+) APCI m/z 382 [M+H]+.

1. customThe free base of bis(2-chloroethyl)-benzlyamine (5.12 g, 19.3 mmol) was prepared
2. washby washing the HCl salt with 1 M NaOH (200 mL)
3. extractionextracting into EtOAc
4. customThe resulting organic phases were dried over NASO4
5. concentrationconcentrated
6. customThe resulting reaction mixture
7. temperatureThe reaction was heated an additional 72 hours
8. customThe cooled reaction mixture
9. customwas quenched with 1 M NaOH (200 mL)
10. extractionextracted into EtOAc (3×200 mL)
11. dry with materialdried over Na2SO4
12. concentrationconcentrated
13. customThe resulting gold oil was purified three times by column chromatography (40% EtOAc/hexanes)

ORD record

ord-41dbe8d3ed704e2e91b90aabacaa93d7

Source dataset

uspto-grants-2001_11

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US06313126B1