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 1913822Notes

Reaction equation

HRID 1913822 reaction equation
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]

Participants

6

Reactant 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

Product 1

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

Reagents, catalysts & solvents 1

HCID 176Acetic AcidSolvent

Procedure

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+).

Workup

  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)

Sources & evidence

ORD record
ord-83de7bef40cc4082b09cb2e651a7d574
Source dataset
uspto-grants-2013_12
Patent number
US08609731B2

Reaction notes

Loading…