Reacción #42978

Ecuación de reacción

(S)-4-(4-chloro-phenyl)-3,3-dimethyl-piperidin-4-ol

potassium carbonate

1-[5-(3-bromo-propylidene)-5,11-dihydro-10-oxa-1-aza-dibenzo[a,d]cyclohepten-7-yl]-ethanone

→

(S)-1-(5-{3-[4-(4-Chloro-phenyl)-4-hydroxy-3,3-dimethyl-piperidin-1-yl]-propylidene}-5,11-dihydro-10-oxa-1-aza-dibenzo[a,d]cyclohepten-7-yl)-ethanone

Disolventes

acetonitrile

water

Condiciones de reacción

Tratamiento posterior

1. 1
   Temperaturawarmed to 50° C.
2. 2
   workup.STIRRINGstirred 13 hours
3. 3
   TemperaturaThe mixture was cooled to room temperature
4. 4
   Otroacetonitrile was removed under reduced pressure
5. 5
   ExtracciónThe aqueous layer was extracted with ethyl acetate (750 mL)
6. 6
   Lavadothe extract was washed with brine
7. 7
   Secadodried over sodium sulfate
8. 8
   Filtraciónfiltered
9. 9
   Concentraciónconcentrated
10. 10
    OtroThe crude residue was purified by silica gel chromatography (3:1 ethyl acetate:hexanes)

Procedimiento

To a suspension of the (S)-4-(4-chloro-phenyl)-3,3-dimethyl-piperidin-4-ol (5.50 g, 22.94 mmol) in acetonitrile (200 mL) and water (50 mL) was added potassium carbonate (7.17 g, 51.9 mmol) followed by solid 1-[5-(3-bromo-propylidene)-5,11-dihydro-10-oxa-1-aza-dibenzo[a,d]cyclohepten-7-yl]-ethanone (6.30 g, 17.3 mmol). The heterogeneous mixture was stirred at room temperature 4 hours, warmed to 50° C. and stirred 13 hours. The mixture was cooled to room temperature and acetonitrile was removed under reduced pressure. The aqueous layer was extracted with ethyl acetate (750 mL) and the extract was washed with brine, dried over sodium sulfate, filtered and concentrated. The crude residue was purified by silica gel chromatography (3:1 ethyl acetate:hexanes) to afford (S)-1-(5-{3-[4-(4-Chloro-phenyl)-4-hydroxy-3,3-dimethyl-piperidin-1-yl]-propylidene}-5,11-dihydro-10-oxa-1-aza-dibenzo[a,d]cyclohepten-7-yl)-ethanone as an off-white solid.

Fuente