Reaktion #217987

Reaktionsgleichung

toluene

2,2,2-trifluoro-1-(7-hydroxy-1,2,4,5-tetrahydro-benzo[d]azepin-3-yl)ethanone

6-chloronicotinamide

K2CO3

→

title compound

Ausbeute 34.1%

6-[3-(2,2,2-Trifluoroacetyl)-2,3,4,5-tetrahydro-1H-benzo[d]azepin-7-yloxy]nicotinamide

Ausbeute 34.1%

Lösungsmittel

DMF

Reaktionsbedingungen

Aufarbeitung

1. 1
   Sonstigebottom equipped with a Dean-Stark trap
2. 2
   TemperaturHeat
3. 3
   Temperaturat reflux for two hours
4. 4
   SonstigeRemove the toluene and DMF as an azeotrope with xylenes
5. 5
   Filtrationfilter
6. 6
   WaschenWash the filter cake with ethyl acetate
7. 7
   EinengenConcentrate the filtrate
8. 8
   Sonstigepurify by flash chromatography
9. 9
   Wascheneluting with 40% ethyl acetate in dichloromethane

Vorschrift

Add 2,2,2-trifluoro-1-(7-hydroxy-1,2,4,5-tetrahydro-benzo[d]azepin-3-yl)ethanone (0.750 g, 2.89 mmol), 6-chloronicotinamide (0.377 g, 2.41 mmol) and K2CO3 (0.833 g, 6.03 mmol) to a round bottom equipped with a Dean-Stark trap. Add toluene (6 mL) and DMF (18 mL). Heat at reflux for two hours. Cool the reaction mixture to 100° C. and stir overnight. Remove the toluene and DMF as an azeotrope with xylenes. Suspend the solid in 5% methanol/ethyl acetate (100 mL) and filter. Wash the filter cake with ethyl acetate. Concentrate the filtrate, then purify by flash chromatography, eluting with 40% ethyl acetate in dichloromethane to give the title compound (0.312 g, 34.0%): MS ES+ 380 (M+H)+; HPLC [YMC-Pack Pro C-18 (150×4.6 mm, S-5 microm), acetonitrile in water containing 0.01% concentrated HCl at 1.0 mL/min, 30-99% over 19 min], tR=8.5 min, 89% purity.

Quelle