반응 #2446557

반응 방정식

NaHCO3

2-methyl-4-(1-(5-phenyl-1,3,4-oxadiazole-2-carbonyl)azetidin-3-yloxy)benzaldehyde

5-Oxa-2-azaspiro[3.4]octane HCl salt

sodium

→

desired product

수율 68.0%

(3-(4-(5-oxa-2-azaspiro[3.4]octan-2-ylmethyl)-3-methylphenoxy)azetidin-1-yl)(5-phenyl-1,3,4-oxadiazol-2-yl)methanone

수율 68.0%

용매

dichloromethane

dichloromethane

dichloromethane

반응 조건

후처리

1. 1
   workup.ADDITIONTriethylamime (0.064 ml, 0.47 mmol) was added
2. 2
   기타The two phases were separated by the use of a phase separator
3. 3
   기타Evaporation of the organic phase
4. 4
   기타afforded a solid residue, which
5. 5
   세척washed with water (20 ml)
6. 6
   여과filtered through a phase separator
7. 7
   기타evaporated
8. 8
   기타The residue was purified by column chromatography (ISOLUTE SI, 20 g/70 ml)
9. 9
   세척eluting with NH3 in MeOH (2M)/dichloromethane (1:99, 2:98)
10. 10
    기타After evaporation of the solvent mixture

실험 절차

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%

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