Reaktion #61495

Reaktionsgleichung

NaHCO3

3-(tert-butyloxycarbonyl)-7-cyano-2,3,4,5-tetrahydro-1H-3-benzazepine

KOH

propargylamine

EDC

HOBT

→

title compound

3-(tert-Butyloxycarbonyl)-2,3,4,5-tetrahydro-1H-3-benzazepine-7-carboxylic acid prop-2-ynyl amide

Lösungsmittel

EtOH

water

dichloromethane

Reaktionsbedingungen

Aufarbeitung

1. 1
   Temperaturwas heated
2. 2
   Temperaturunder reflux for 24 h
3. 3
   Temperaturto cool
4. 4
   Sonstigeevaporated in vacuo
5. 5
   workup.DISSOLUTIONthe residue redissolved in water (150 ml)
6. 6
   Filtrationthe precipitate filtered
7. 7
   Sonstigedried
8. 8
   Sonstigethe organic layer separated
9. 9
   ExtraktionThe aqueous layer was re-extracted with dichloromethane
10. 10
    Sonstigethe combined organic layers dried
11. 11
    Sonstigeevaporated in vacuo
12. 12
    SonstigeThe residue was purified by silica gel chromatography (gradient elution, hexane/ethyl acetate)

Vorschrift

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.

Quelle