تفاعل #2446557

ord-bcb7305dfce246a2bd5a8f031e362a52

ظروف التفاعل

الظروف التفصيلية
See reaction.notes.procedure_details.

المعالجة

  1. 1
    workup.ADDITIONTriethylamime (0.064 ml, 0.47 mmol) was added
  2. 2
    أخرىThe two phases were separated by the use of a phase separator
  3. 3
    أخرىEvaporation of the organic phase
  4. 4
    أخرىafforded a solid residue, which
  5. 5
    غسيلwashed with water (20 ml)
  6. 6
    ترشيحfiltered through a phase separator
  7. 7
    أخرىevaporated
  8. 8
    أخرىThe residue was purified by column chromatography (ISOLUTE SI, 20 g/70 ml)
  9. 9
    غسيلeluting with NH3 in MeOH (2M)/dichloromethane (1:99, 2:98)
  10. 10
    أخرىAfter evaporation of the solvent mixture

الإجراء التجريبي

5-Oxa-2-azaspiro[3.4]octane HCl salt (0.064 g, 0.43 mmol) was dissolved in dichloromethane (2 ml). Triethylamime (0.064 ml, 0.47 mmol) was added, followed by 2-methyl-4-(1-(5-phenyl-1,3,4-oxadiazole-2-carbonyl)azetidin-3-yloxy)benzaldehyde (0.13 g, 0.36 mmol) and finally sodium triacetoxyhydroborate (0.152 g, 0.72 mmol). The resulting mixture was stirred at ambient temperature overnight. The reaction mixture was the diluted with dichloromethane (10 ml) and shaken with NaHCO3 (sat. 3 ml). The two phases were separated by the use of a phase separator. Evaporation of the organic phase afforded a solid residue, which again was dissolved in dichloromethane (ca. 20 ml), washed with water (20 ml), filtered through a phase separator and evaporated. The residue was purified by column chromatography (ISOLUTE SI, 20 g/70 ml), eluting with NH3 in MeOH (2M)/dichloromethane (1:99, 2:98). After evaporation of the solvent mixture, 112 mg (68%) of the desired product was obtained as a solid. 1H NMR (400 MHz, CDCl3) δ 1.91 (p, 2H), 2.14 (t, 2H), 2.33 (s, 3H), 3.15 (d, 2H), 3.39 (d, 2H), 3.59 (s, 2H), 3.82 (t, 2H), 4.35 (dd, 1H), 4.67 (dd, 1H), 4.74-4.8 (m, 1H), 5.11 (ddt, 2H), 6.57 (dd, 1H), 6.62 (d, 1H), 7.22 (d, 1H), 7.53-7.65 (m, 3H), 8.16-8.23 (m, 2H). MS (APCI+) m/z 461.3 [M+H]+, LC purity: 99%

المصدر

DOI: 10.6084/m9.figshare.5104873.v1براءة الاختراع: US08685958B2uspto-grants-2014_04