反应详情

A mixture of 3-(tert-butyloxycarbonyl)-7-cyano-2,3,4,5-tetrahydro-1H-3-benzazepine (10 g, 37 mmol) and KOH (4.1 g, 73 mmol) in EtOH (100 ml) and water (20 ml) was heated under reflux for 24 h. Mixture allowed to cool and evaporated in vacuo and the residue redissolved in water (150 ml). The solution was acidified to pH4 and the precipitate filtered and dried. The crude acid (5 g, 17 mmol) was then dissolved in dichloromethane (100 ml), under Argon and propargylamine (0.77 g, 14 mmol), EDC (2.9 g 15 mmol) and HOBT (200 mg) added and the reaction stirred for 18 h. Saturated NaHCO3 solution (100 ml) was added and the organic layer separated. The aqueous layer was re-extracted with dichloromethane and the combined organic layers dried and evaporated in vacuo. The residue was purified by silica gel chromatography (gradient elution, hexane/ethyl acetate) to give the title compound (3.8 g) as a colourless solid.

1. temperaturewas heated
2. temperatureunder reflux for 24 h
3. temperatureto cool
4. customevaporated in vacuo
5. dissolutionthe residue redissolved in water (150 ml)
6. filtrationthe precipitate filtered
7. customdried
8. customthe organic layer separated
9. extractionThe aqueous layer was re-extracted with dichloromethane
10. customthe combined organic layers dried
11. customevaporated in vacuo
12. customThe residue was purified by silica gel chromatography (gradient elution, hexane/ethyl acetate)