2,3,4,5-TETRAHYDRO-BENZO[C]AZEPIN-1-ONE

Chemical Properties

White to beige crystalline powder

Synthesis

General procedure for the synthesis of 2,3,4,5-tetrahydro-1H-2-benzazepin-1-one from 1-tetrahydronaphthalenone: 2.72 g (41.8 mmol) of sodium azide was added batchwise to a solution of concentrated hydrochloric acid (75 mL) containing 6.11 g (41.8 mmol) of 3,4-dihydronaphthalen-1(2H)-one and the reaction was carried out at 0 °C. Subsequently, the reaction was eluted with hydrochloric acid (75 mL) at 0 °C for 1 h. Stirring was continued at 0 °C for 30 min, then slowly warmed to room temperature and the reaction lasted for 16 hours. Upon completion of the reaction, the reaction mixture was poured into ice water and the pH was adjusted with potassium carbonate to 9. The aqueous phase was extracted with dichloromethane (DCM), the organic phases were combined and dried with anhydrous magnesium sulfate (MgSO), filtered and concentrated under reduced pressure. The residue was purified by recrystallization from hexane. Further purification by column chromatography (silica gel, eluent hexane/ethyl acetate = 1:2) afforded 1.8 g (11.1 mmol, 27% yield) of the target product 2,3,4,5-tetrahydro-1H-2-benzazepin-1-one.

References

[1] Angewandte Chemie - International Edition, 2018, vol. 57, # 38, p. 12347 - 12351
[2] Angew. Chem., 2018, vol. 130, # 38, p. 12527 - 12531,5
[3] ACS Medicinal Chemistry Letters, 2012, vol. 3, # 11, p. 914 - 919
[4] Journal of Medicinal Chemistry, 2015, vol. 58, # 13, p. 5287 - 5307
[5] Angewandte Chemie - International Edition, 2017, vol. 56, # 13, p. 3655 - 3659