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

HRID 1477507노트

반응식

HRID 1477507 반응식
[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

참가 물질

5

반응물 3

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

생성물 1

HCID 86699315tert-butyl (1R,5R)-1-(3-methyl-1,2,4-oxadiazol-5-yl)-3-azabicyclo[3.1.0]hexane-3-carboxylate수율 56.5%

시약·촉매·용매 1

HCID 73012-Methyltetrahydrofuran용매

실험 절차

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).

후처리

  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

출처 및 근거

ORD 기록
ord-470a92df52dd44649a8aeeaded6edabb
출처 데이터셋
uspto-grants-2016_08
특허 번호
US09403806B1

반응 노트

불러오는 중…