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

HRID 716222

반응식

HRID 716222 반응식
F[C:2]1[CH:11]=[CH:10][C:5]([C:6]([NH:8][CH3:9])=[O:7])=[CH:4][CH:3]=1.[NH:12]1[CH2:17][CH2:16][NH:15][CH2:14][CH2:13]1>CS(C)=O>[CH3:9][NH:8][C:6](=[O:7])[C:5]1[CH:10]=[CH:11][C:2]([N:12]2[CH2:17][CH2:16][NH:15][CH2:14][CH2:13]2)=[CH:3][CH:4]=1

참가 물질

4

반응물 2

HCID 4837PiperazineHCID 40742474-fluoro-N-methylbenzamide

생성물 1

HCID 28749530N-methyl-4-(piperazin-1-yl)benzamide수율 65.7%

시약·촉매·용매 1

HCID 679Dimethyl Sulfoxide용매

반응 조건

온도
120 °C

실험 절차

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 H2O (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. 1H NMR (400 MHz, DMSO-d6) δ ppm 2.29 (br. s., 1H) 2.74 (d, J=4.55 Hz, 3H) 2.77-2.86 (m, 4H) 3.08-3.18 (m, 4H) 6.91 (m, 2H) 7.69 (m, 2H) 8.13 (q, J=4.04 Hz, 1H). ESI-MS: m/z 220.2 (M+H)+. mp=153.9-156.5° C.

후처리

  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 H2O (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

출처 및 근거

ORD 기록
ord-10801e4217444db5896293039d93abd2
출처 데이터셋
uspto-grants-2015_11
특허 번호
US09187497B2

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