반응 #81541

ord-8c00a7cd75684bf6beee7bc795341495

용매

반응 조건

상세 조건
See reaction.notes.procedure_details.

후처리

  1. 1
    온도was heated
  2. 2
    온도at reflux for 60 h
  3. 3
    온도the mixture heated
  4. 4
    온도at reflux for a further 18 h
  5. 5
    온도cooled to 0° C.
  6. 6
    여과filtered
  7. 7
    기타The solid was collected
  8. 8
    세척washed with anhydrous ether
  9. 9
    기타then partitioned between dichloromethane (200 ml) and sodium hydroxide solution (1M, 150 ml)
  10. 10
    기타The organic layer was separated
  11. 11
    세척the aqueous phase washed once more with dichloromethane (200 ml)
  12. 12
    건조The combined organic layers were dried (K2CO3)
  13. 13
    기타evaporated in vacuo
  14. 14
    기타The resultant residue was chromatographed on silica gel
  15. 15
    기타to afford an orange oil
  16. 16
    기타The oil crystallised
  17. 17
    기타the resultant solid was triturated with petrol (60/80)

실험 절차

A mixture of N-methylbis (2-chloroethyl)amine hydrochloride (9.8 g) and 3-nitroaniline (7.0 g) in 1-butanol (100 ml) was heated at reflux for 60 h then cooled to room temperature. Sodium carbonate (2.8 g) was then added and the mixture heated at reflux for a further 18 h, then cooled to 0° C. and filtered. The solid was collected, washed with anhydrous ether then partitioned between dichloromethane (200 ml) and sodium hydroxide solution (1M, 150 ml). The organic layer was separated and the aqueous phase washed once more with dichloromethane (200 ml). The combined organic layers were dried (K2CO3) and evaporated in vacuo. The resultant residue was chromatographed on silica gel, using dichloromethane:methanol (96:4) as the eluant, to afford an orange oil. The oil crystallised on standing and the resultant solid was triturated with petrol (60/80) to give the desired piperazine (5.64 g). 1H NMR (360 MHz, CDCl3) δ2.37 (3H, s), 2.58 (4H, t, J=5 Hz), 3.30 (4H, t, J=5 Hz), 7.18 (1H, dd, J=9 and 3 Hz), 7.35 (1H, t, J=8 Hz), 7.64 (1H, dd, J=9 and 2 Hz), 7.71 (1H, d, J=2 Hz). MS (CI, NH3) 222 (M+1).

출처

DOI: 10.6084/m9.figshare.5104873.v1특허: US05618812uspto-grants-1997_04