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

HRID 874527

반응식

HRID 874527 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 fritted 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., 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.

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 fritted funnel
  15. washrinsed with H2O (3×10 mL)
  16. temperatureAdded NaCl (200.1 g) to the filtrate, cooled on ice
  17. filtrationfiltered
  18. washrinsed with cold H2O (3×25 mL)
  19. customdried the resulting solid in vacuo
  20. stirringRe-suspended the purified product in H2O (30 mL), stirred for 30 min at 23° C.
  21. filtrationfiltered
  22. washrinsed with H2O (3×5 mL)
  23. customdried the resulting solid in vacuo
  24. stirringagitated for 10 min
  25. customdried in vacuo

출처 및 근거

ORD 기록
ord-6074812166e2447da15d42ef34c2a660
출처 데이터셋
uspto-grants-2015_03
특허 번호
US08980902B2

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