반응 #220782

ord-5b03f26ee07c46b0b07c12e9ad32c1b1

반응 조건

온도
25°CELSIUS
상세 조건
See reaction.notes.procedure_details.

후처리

  1. 1
    기타The resulting reaction mixture
  2. 2
    추출The obtained mixture was extracted with dichloromethane (50 mLX 2)
  3. 3
    세척washed with H2O (50 mL×2) and brine (50 mL)
  4. 4
    건조dried (over MgSO4)
  5. 5
    농축concentrated
  6. 6
    기타to thereby afford a yellow oil
  7. 7
    기타The obtained crude product
  8. 8
    기타was purified by column chromatography (SiO2,70% ethyl acetate-hexane)

실험 절차

N-[3-(Trifluoromethyl)benzoyl]glycine (4.22 g, 17.0 mmol), EDCI (4.25 g, 22.1 mmol), 1-hydroxybenzotriazole hydrate (2.99 g, 22.1 mmol) and triethylamine (1.72 g) were added to an anhydrous dichloromethane (200 mL) solution of 1-(tert-butoxycarbonyl)-4-(aminomethyl)piperidine (4.03 g). The resulting reaction mixture was stirred at 25° C. for 20 hours, and H2O (100 mL) was then added to the mixture. The obtained mixture was extracted with dichloromethane (50 mLX 2). The extracts were combined, washed with H2O (50 mL×2) and brine (50 mL), dried (over MgSO4) and concentrated to thereby afford a yellow oil. The obtained crude product was purified by column chromatography (SiO2,70% ethyl acetate-hexane) to provide 1-(tert-butoxycarbonyl)-4-[[N-(3-(trifluoromethyl)benzoyl)glycyl]aminomethyl]piperidine as a white solid (6.39 g, 85%). 1H NMR (CDCl3, 300 MHz) δ 1.4 (s, 9H), 1.0-1.8 (m, 5H), 2.6-2.8 (m, 2H), 3.15-3.3 (m, 2H), 4.0-4.3 (m, 4H), 6.6-6.7 (m, 1H), 7.64 (s, 1H), 7.60 (dd, 1H, J=7.2, 7.2 Hz), 7.79 (d, 1H, J=7.2 Hz), 8.0 (d, 1H, J=7.2 Hz), 8.11 (s, 1H). The purity was determined by RPLC/MS (97%). ESI/MS m/e 444.3 (M++H, C21H28N3O4).

출처

DOI: 10.6084/m9.figshare.5104873.v1특허: US07390830B1uspto-grants-2008_06