Ammonium Chloride → Samidorphan

HRID 1043976ノート

反応式

HRID 1043976 の反応式
[CH:1]1([CH2:4][N:5]2[CH2:25][CH2:24][C@:12]34[C:13]5[C:14]6[O:23][C@H:11]3[C:10](=[O:26])[CH2:9][CH2:8][C@@:7]4([OH:27])[C@H:6]2[CH2:19][C:18]=5[CH:17]=[CH:16][C:15]=6[C:20]([NH2:22])=[O:21])[CH2:3][CH2:2]1.[Cl-].[NH4+]>C(O)C.[Zn]>[CH:1]1([CH2:4][N:5]2[CH2:25][CH2:24][C@@:12]34[C:13]5[C:14]([OH:23])=[C:15]([C:20]([NH2:22])=[O:21])[CH:16]=[CH:17][C:18]=5[CH2:19][C@@H:6]2[C@:7]3([OH:27])[CH2:8][CH2:9][C:10](=[O:26])[CH2:11]4)[CH2:3][CH2:2]1

参加物

5

反応物 2

HCID 25517Ammonium ChlorideHCID 100219463-Desoxy-3-carboxamidonaltrexone

生成物 1

HCID 11667832Samidorphan収率 48%

試薬・触媒・溶媒 2

HCID 23994Zinc触媒HCID 702Ethanol溶媒

反応条件

温度
90 °C

実験手順

A mixture of (5a)-17-(cyclopropylmethyl)-14-hydroxy-6-oxo-4,5-epoxymorphinan-3-carboxamide [P3] (3.0 g, 8.15 mmol), Zinc powder (2.67 g, 40.76 mmol), and ammonium chloride (3.05 g, 57.1 mmol) in ethanol (500 mL) was heated at 90° C. for 1 hour. The reaction mixture was allowed to return to room temperature then filtered. The residual solid was washed with excess methanol (500 mL) followed by 7% ammonium hydroxide (100 mL). The combined filtrates were concentrated under reduced pressure and the residue partitioned between dichloromethane and 7% ammonium hydroxide solution. The aqueous phase was washed with further DCM and the combined organic layers dried (MgSO4). Filtration and removal of the solvent under reduced pressure giving 17-(cyclopropylmethyl)-4,14-dihydroxy-6-oxomorphinan-3-carboxamide [P4] (1.45 g, 48% yield); LC/MS (r.t. 10.7 minutes [5 to 95% B]), 371 (M+H)+.

後処理

  1. customto return to room temperature
  2. filtrationthen filtered
  3. washThe residual solid was washed with excess methanol (500 mL)
  4. concentrationThe combined filtrates were concentrated under reduced pressure
  5. customthe residue partitioned between dichloromethane and 7% ammonium hydroxide solution
  6. washThe aqueous phase was washed with further DCM
  7. dry with materialthe combined organic layers dried (MgSO4)
  8. filtrationFiltration and removal of the solvent under reduced pressure

出典と根拠

ORDレコード
ord-9ee7f6592190481788fd87f399e35a76
出典データセット
uspto-grants-2013_10
特許番号
US08563572B2

反応ノート

読み込み中…