Sulfuric Acid → N-[(S)-6-(1-Amino-1-methylethyl)-1,2,3,4-tetrahydronaphthalen-2-yl]-4-[(S)-1-(tetrahydrofuran-2-yl)methoxy]benzamide

HRID 1913822ノート

反応式

HRID 1913822 の反応式
O[C:2]([C:5]1[CH:6]=[C:7]2[C:12](=[CH:13][CH:14]=1)[CH2:11][C@@H:10]([NH:15][C:16](=[O:30])[C:17]1[CH:22]=[CH:21][C:20]([O:23][CH2:24][C@@H:25]3[CH2:29][CH2:28][CH2:27][O:26]3)=[CH:19][CH:18]=1)[CH2:9][CH2:8]2)([CH3:4])[CH3:3].C[Si](C#[N:36])(C)C.S(=O)(=O)(O)O.[OH-].[Na+]>C(O)(=O)C>[NH2:36][C:2]([C:5]1[CH:6]=[C:7]2[C:12](=[CH:13][CH:14]=1)[CH2:11][C@@H:10]([NH:15][C:16](=[O:30])[C:17]1[CH:22]=[CH:21][C:20]([O:23][CH2:24][C@@H:25]3[CH2:29][CH2:28][CH2:27][O:26]3)=[CH:19][CH:18]=1)[CH2:9][CH2:8]2)([CH3:4])[CH3:3]

参加物

6

反応物 4

HCID 1118Sulfuric AcidHCID 14798Sodium HydroxideHCID 82115Trimethylsilyl cyanideHCID 67545052N-[(S)-6-(1-hydroxy-1-methylethyl)-1,2,3,4-tetrahydronaphthalen-2-yl]-4-[(S)-1-(tetrahydrofuran-2-yl)methoxy]benzamide

生成物 1

HCID 59505956N-[(S)-6-(1-Amino-1-methylethyl)-1,2,3,4-tetrahydronaphthalen-2-yl]-4-[(S)-1-(tetrahydrofuran-2-yl)methoxy]benzamide

試薬・触媒・溶媒 1

HCID 176Acetic Acid溶媒

実験手順

A mixture, cooled to 0° C., of N-[(S)-6-(1-hydroxy-1-methylethyl)-1,2,3,4-tetrahydronaphthalen-2-yl]-4-[(S)-1-(tetrahydrofuran-2-yl)methoxy]benzamide (0.30 g), glacial acetic acid (1 ml) and trimethylsilyl cyanide (145 mg) was admixed dropwise with sulfuric acid (1.2 ml; 96%). The cooling bath was removed and the mixture was stirred for another 12 hours. The reaction mixture was diluted with water and extracted with ethyl acetate. The organic phase was washed with sodium chloride solution, dried over sodium sulfate and concentrated. The residue was taken up in 1,4-dioxane (20 ml) and boiled at reflux with dilute hydrochloric acid for 30 minutes. The reaction mixture was washed with ethyl acetate and basified with concentrated sodium hydroxide solution. Extraction with dichloromethane gave rise to an organic phase which was dried over sodium sulfate and concentrated. (Alternatively, the hydrolysis of the intermediate formamide can also be achieved by boiling with sodium hydroxide solution.) The product was thus obtained with the molecular weight of 408.55 (C25H32N2O3); MS (ESI): 409 (M+H+).

後処理

  1. customThe cooling bath was removed
  2. additionThe reaction mixture was diluted with water
  3. extractionextracted with ethyl acetate
  4. washThe organic phase was washed with sodium chloride solution
  5. dry with materialdried over sodium sulfate
  6. concentrationconcentrated
  7. temperatureat reflux with dilute hydrochloric acid for 30 minutes
  8. washThe reaction mixture was washed with ethyl acetate and basified with concentrated sodium hydroxide solution
  9. extractionExtraction with dichloromethane
  10. customgave rise to an organic phase which
  11. dry with materialwas dried over sodium sulfate
  12. concentrationconcentrated
  13. custom(Alternatively, the hydrolysis of the intermediate formamide
  14. custom) The product was thus obtained with the molecular weight of 408.55 (C25H32N2O3)

出典と根拠

ORDレコード
ord-83de7bef40cc4082b09cb2e651a7d574
出典データセット
uspto-grants-2013_12
特許番号
US08609731B2

反応ノート

読み込み中…