Reaktion #63581

Reaktionsgleichung

2-(3-bromopropoxy)tetrahydro-2H-pyran

ammonium chloride

2-propanone CO2

ammonia

1-(4-fluorophenyl)-1,3-dihydroisobenzofuran

2-propanone CO2

sodium

→

1-(4-fluorophenyl)-1,3-dihydro-1-[3-(tetrahydro-2H-pyran-2-yloxy)propyl]isobenzofuran

Lösungsmittel

1,1'-oxybisethane

water

1,1'-oxybisethane

Reaktionsbedingungen

Aufarbeitung

1. 1
   workup.STIRRINGAfter stirring for 20 minutes
2. 2
   Temperaturwhile still cooling
3. 3
   workup.STIRRINGUpon completion, stirring
4. 4
   TemperaturWithout cooling and without nitrogen, there
5. 5
   workup.STIRRINGstirring
6. 6
   SonstigeThe layers were separated
7. 7
   Extraktionthe aqueous phase was extracted twice with 1,1'-oxybisethane
8. 8
   WaschenThe combined organic phases were washed with water
9. 9
   Sonstigedried
10. 10
    Filtrationfiltered
11. 11
    Sonstigeevaporated
12. 12
    SonstigeThe residue was purified by column-chromatography over silica gel using
13. 13
    workup.ADDITIONa mixture of trichloromethane and methanol (99.5:0.5 by volume) as eluent
14. 14
    SonstigeThe second fraction was collected
15. 15
    Sonstigethe eluent was evaporated

Vorschrift

To a stirred and cooled (2-propanone/CO2 -bath) amount of 1080 parts of ammonia was added 1 part of iron (III)chloride, followed by the portionwise addition of 7.7 parts of sodium under nitrogen atmosphere. After stirring for 20 minutes, there was added dropwise a solution of 64.5 parts of 1-(4-fluorophenyl)-1,3-dihydroisobenzofuran in 105 parts of 1,1'-oxybisethane while still cooling. Then there was added dropwise a solution of 75 parts of 2-(3-bromopropoxy)tetrahydro-2H-pyran in 37 parts of 1,1-oxybisethane. Upon completion, stirring was continued for 2 hours under nitrogen atmosphere in a 2-propanone/CO2 -bath. Without cooling and without nitrogen, there were added dropwise slowly 490 parts of 1,1'-oxybisethane and stirring was continued overnight at room temperature. 225 Parts of a saturate ammonium chloride solution were added dropwise followed by the addition of 200 parts of water. The layers were separated and the aqueous phase was extracted twice with 1,1'-oxybisethane. The combined organic phases were washed with water, dried, filtered and evaporated. The residue was purified by column-chromatography over silica gel using a mixture of trichloromethane and methanol (99.5:0.5 by volume) as eluent. The second fraction was collected and the eluent was evaporated, yielding 39.6 parts of 1-(4-fluorophenyl)-1,3-dihydro-1-[3-(tetrahydro-2H-pyran-2-yloxy)propyl]isobenzofuran as a residue (intermediate 10).

Quelle