Piperazine → N-methyl-4-(piperazin-1-yl)benzamide

Temperatur

120 °C

To a solution of 4-fluoro-N-methylbenzamide (6 g, 39.2 mmol) in DMSO (Volume: 24.0 mL) was added piperazine (16.87 g, 196 mmol) at 23° C. The reaction was stirred at 120° C. for 68 hr. The reaction mixture was poured into ice (261 g) and the reaction vessel was rinsed with H2O (˜50 mL). Next, celite (30 g) was added to aid the filtration. The resulting suspension was warmed to 100° C., cooled to ˜40° C., filtered, and rinsed with warm H20 (4×50 mL). The resulting solid was dried in vacuo. The filtrate was stirred at room temperature overnight affording a suspension. The suspension was filtered, rinsed with H2O (3×25 mL), and the resulting solid was dried in vacuo. The cloudy filtrate was filtered once again through a medium fitted funnel and rinsed with H2O (3×10 mL). Added NaCl (200.1 g) to the filtrate, cooled on ice, filtered, rinsed with cold H2O (3×25 mL), and dried the resulting solid in vacuo. Re-suspended the purified product in H2O (30 mL), stirred for 30 min at 23° C., filtered, rinsed with H2O (3×5 mL), and dried the resulting solid in vacuo. The purified product was re-suspended in ACN (25 mL), agitated for 10 min, and dried in vacuo. This procedure was repeated three times to provide N-methyl-4-(piperazin-1-yl)benzamide (5.64 g, 25.7 mmol, 65.7% yield) as a white solid. 1 H NMR (400 MHz, DMSO-d6) δ ppm 2.29 (br. s., 1 H) 2.74 (d, J=4.55 Hz, 3 H) 2.77-2.86 (m, 4 H) 3.08-3.18 (m, 4 H) 6.91 (m, 2 H) 7.69 (m, 2 H) 8.13 (q, J=4.04 Hz, 1 H). ESI-MS: m/z 220.2 (M+H)+. mp=153.9-156.5° C.

1. washthe reaction vessel was rinsed with H2O (˜50 mL)
2. additionNext, celite (30 g) was added
3. filtrationthe filtration
4. temperatureThe resulting suspension was warmed to 100° C.
5. temperaturecooled to ˜40° C.
6. filtrationfiltered
7. washrinsed with warm H20 (4×50 mL)
8. customThe resulting solid was dried in vacuo
9. stirringThe filtrate was stirred at room temperature overnight
10. customaffording a suspension
11. filtrationThe suspension was filtered
12. washrinsed with H2O (3×25 mL)
13. customthe resulting solid was dried in vacuo
14. filtrationThe cloudy filtrate was filtered once again through a medium
15. customfitted funnel
16. washrinsed with H2O (3×10 mL)
17. temperatureAdded NaCl (200.1 g) to the filtrate, cooled on ice
18. filtrationfiltered
19. washrinsed with cold H2O (3×25 mL)
20. customdried the resulting solid in vacuo
21. stirringRe-suspended the purified product in H2O (30 mL), stirred for 30 min at 23° C.
22. filtrationfiltered
23. washrinsed with H2O (3×5 mL)
24. customdried the resulting solid in vacuo
25. stirringagitated for 10 min
26. customdried in vacuo

ORD-Eintrag

ord-67fd24bae1e54253a4d87ba61cc7543e

Quelldatensatz

uspto-grants-2014_09

DOI

10.6084/m9.figshare.5104873.v1

Patentnummer

US08822470B2