N-Hydroxyacetamidine → tert-butyl (1R,5R)-1-(3-methyl-1,2,4-oxadiazol-5-yl)-3-azabicyclo[3.1.0]hexane-3-carboxylate

HRID 1477507Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1477507
[C:1](=[N:4][OH:5])([NH2:3])[CH3:2].C[O-].[Na+].[C@:9]12([C:22](OCC)=O)[CH2:14][C@H:13]1[CH2:12][N:11]([C:15]([O:17][C:18]([CH3:21])([CH3:20])[CH3:19])=[O:16])[CH2:10]2>CC1CCCO1>[CH3:2][C:1]1[N:3]=[C:22]([C@:9]23[CH2:14][C@H:13]2[CH2:12][N:11]([C:15]([O:17][C:18]([CH3:21])([CH3:20])[CH3:19])=[O:16])[CH2:10]3)[O:5][N:4]=1

Komponenten

5

Edukt 3

HCID 30926N-HydroxyacetamidineHCID 10942334Sodium MethoxideHCID 866993163-tert-butyl 1-ethyl (1R,5R)-3-azabicyclo(3.1.0)hexane-1,3-dicarboxylate

Produkt 1

HCID 86699315tert-butyl (1R,5R)-1-(3-methyl-1,2,4-oxadiazol-5-yl)-3-azabicyclo[3.1.0]hexane-3-carboxylateAusbeute 56,5 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 73012-MethyltetrahydrofuranLösungsmittel

Versuchsvorschrift

2-Methyl-tetrahydrofuran (40 mL), acetamide oxime (0.93 g, 0.0125 mol) and sodium methoxide (1.1 g, 0.020 mol) were added to (1R,5R)-3-tert-butyl 1-ethyl 3-azabicyclo[3.1.0]hexane-1,3-dicarboxylate (142) (1.27 g, 0.0050 mol) and the mixture was heated to reflux for 3 hrs. Upon cooling the suspension was partitioned between ethyl acetate (100 mL) and water (25 mL). The organic layer was washed with water (25 mL), saturated sodium chloride (25 mL) and dried over Na2SO4. The mixture was concentrated and the residue was chromatographed over 25 g of silica gel with 15-25% ethyl acetate/hexanes, to obtain 0.75 g of clear colorless oil. MS (ESI) m/z 304 [M+K]+. 1H NMR (CDCl3) δ 1.16-1.17 (m, 1 H), 1.46 (s, 9 H), 1.60 (s, 1 H), 1.72-1.75 (m, 1 H), 2.36 (s, 3 H), 3.49-3.51 (m, 1 H), 3.65-3.79 (dd, 1 H), 3.91-4.00 (m, 2 H).

Aufarbeitung

  1. temperaturethe mixture was heated
  2. temperatureto reflux for 3 hrs
  3. temperatureUpon cooling the suspension
  4. customwas partitioned between ethyl acetate (100 mL) and water (25 mL)
  5. washThe organic layer was washed with water (25 mL), saturated sodium chloride (25 mL)
  6. dry with materialdried over Na2SO4
  7. concentrationThe mixture was concentrated
  8. customthe residue was chromatographed over 25 g of silica gel with 15-25% ethyl acetate/hexanes

Quellen und Nachweise

ORD-Eintrag
ord-470a92df52dd44649a8aeeaded6edabb
Quelldatensatz
uspto-grants-2016_08
Patentnummer
US09403806B1

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