Ammonium Chloride → 4-(4-(4-Chlorophenyl)piperazin-1-yl)butanimidamide

Trimethylaluminium (2M solution in toluene, 12.32 ml, 24.64 mmol) was added dropwise to a suspension of ammonium chloride (1.32 g, 24.64 mmol) in dry toluene (20 ml) over a period of 20 min at 0° C. under nitrogen atmosphere. The resulting mixture was allowed to stir for 15 min at room temperature. To this was added dropwise a solution of 4-(4-(4-chlorophenyl) piperazin-1-yl)butanenitrile (1.3 g, 4.93 mmol) in dry toluene (10 ml) over a period of 10 min and the reaction mixture was heated at about 90° C. - about 100° C. for 15 h under stirring. The reaction mixture was cooled to 25° C., slowly poured into a slurry of silica gel (100-200 mesh, 30 g) in chloroform (100 ml) and was stirred for 10 min. The silica was filtered through celite and washed with methanol (3 ×50 ml). Combined filtrate was evaporated to obtain a crude solid which was dissolved in 10% hydrochloric acid (100 ml) and washed with diethyl ether (2 x 25 ml). To the resulting aqueous layer was added saturated aqueous solution of sodium hydroxide (30 ml) to bring the pH between 13 and 14. The aqueous layer was extracted with chloroform (3 ×100 ml). The combined organic layer was dried over anhydrous sodium sulphate. The solvent in the organic was evaporated under reduced pressure to obtain the title compound (1.1 g, 79% yield).

1. temperaturethe reaction mixture was heated at about 90° C. - about 100° C. for 15 h
2. stirringunder stirring
3. temperatureThe reaction mixture was cooled to 25° C.
4. stirringwas stirred for 10 min
5. filtrationThe silica was filtered through celite
6. washwashed with methanol (3 ×50 ml)
7. customCombined filtrate was evaporated
8. customto obtain a crude solid which
9. washwashed with diethyl ether (2 x 25 ml)
10. additionTo the resulting aqueous layer was added saturated aqueous solution of sodium hydroxide (30 ml)
11. extractionThe aqueous layer was extracted with chloroform (3 ×100 ml)
12. dry with materialThe combined organic layer was dried over anhydrous sodium sulphate
13. customThe solvent in the organic was evaporated under reduced pressure

ORD-Eintrag

ord-2c1a1c4f93704510ab2f306669f068c3

Quelldatensatz

uspto-grants-2016_06

DOI

10.6084/m9.figshare.5104873.v1

Patentnummer

US09359367B2