反应详情

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 saturated 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 93).

1. stirringAfter stirring for 20 minutes
2. temperaturewhile still cooling
3. stirringUpon completion, stirring
4. temperatureWithout cooling and without nitrogen, there
5. stirringstirring
6. customThe layers were separated
7. extractionthe aqueous phase was extracted twice with 1,1'-oxybisethane
8. washThe combined organic phases were washed with water
9. customdried
10. filtrationfiltered
11. customevaporated
12. customThe residue was purified by column-chromatography over silica gel using
13. additiona mixture of trichloromethane and methanol (99.5:0.5 by volume) as eluent
14. customThe second fraction was collected
15. customthe eluent was evaporated