Hydrogen Peroxide → 3-Desoxy-3-carboxamidonaltrexone

HRID 1043975노트

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HRID 1043975 반응식
[CH:1]1([CH2:4][N:5]2[CH2:24][CH2:23][C@:12]34[C:13]5[C:14]6[O:22][C@H:11]3[C:10](=[O:25])[CH2:9][CH2:8][C@@:7]4([OH:26])[C@H:6]2[CH2:19][C:18]=5[CH:17]=[CH:16][C:15]=6[C:20]#[N:21])[CH2:3][CH2:2]1.C(=O)([O-])[O-:28].[K+].[K+].OO>CS(C)=O.C(Cl)Cl>[CH:1]1([CH2:4][N:5]2[CH2:24][CH2:23][C@:12]34[C:13]5[C:14]6[O:22][C@H:11]3[C:10](=[O:25])[CH2:9][CH2:8][C@@:7]4([OH:26])[C@H:6]2[CH2:19][C:18]=5[CH:17]=[CH:16][C:15]=6[C:20]([NH2:21])=[O:28])[CH2:3][CH2:2]1

참가 물질

6

반응물 3

HCID 784Hydrogen PeroxideHCID 11430Potassium CarbonateHCID 15425895HCID 15425895, 화합물

생성물 1

HCID 100219463-Desoxy-3-carboxamidonaltrexone수율 71.4%

시약·촉매·용매 2

HCID 679Dimethyl Sulfoxide용매HCID 6344Dichloromethane용매

실험 절차

To an ice/water cooled suspension of (5a)-17-(cyclopropylmethyl)-14-hydroxy-6-oxo-4,5-epoxymorphinan-3-carbonitrile [P2] (6.0 g, 17.1 mmol) and potassium carbonate (7.09 g, 51.37 mmol) in DMSO (120 mL) was added hydrogen peroxide (25 mL, 35 wt. % in H2O) drop wise at a rate to ensure the temperature remained below 20° C. The mixture was stirred for 2 hours then diluted with DCM (800 mL). The solution was washed with water (3×500 mL) before the organic phase was dried (MgSO4). Filtration and removal of the solvent under reduced pressure gave crude product that was purified by trituration with methanol giving (5a)-17-(cyclopropylmethyl)-14-hydroxy-6-oxo-4,5-epoxymorphinan-3-carboxamide [P3] (4.50 g, 71% yield); LC/MS (r.t. 10.1 minutes [5 to 95% B]), 369 (M+H)+.

후처리

  1. customremained below 20° C
  2. washThe solution was washed with water (3×500 mL) before the organic phase
  3. dry with materialwas dried (MgSO4)
  4. filtrationFiltration and removal of the solvent under reduced pressure
  5. customgave crude product that
  6. customwas purified by trituration with methanol

출처 및 근거

ORD 기록
ord-631417747ebd4975a9b8a0598f147568
출처 데이터셋
uspto-grants-2013_10
특허 번호
US08563572B2

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