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

HRID 35303

Reaktionsgleichung

Reaktionsgleichung von HRID 35303
CC(=O)C.C(=O)=O.N.[Na].[F:10][C:11]1[CH:16]=[CH:15][C:14]([CH:17]2[C:25]3[C:20](=[CH:21][CH:22]=[CH:23][CH:24]=3)[CH2:19][O:18]2)=[CH:13][CH:12]=1.Br[CH2:27][CH2:28][CH2:29][O:30][CH:31]1[CH2:36][CH2:35][CH2:34][CH2:33][O:32]1.[Cl-].[NH4+]>[Fe](Cl)(Cl)Cl.O.O(CC)CC>[F:10][C:11]1[CH:16]=[CH:15][C:14]([C:17]2([CH2:27][CH2:28][CH2:29][O:30][CH:31]3[CH2:36][CH2:35][CH2:34][CH2:33][O:32]3)[C:25]3[C:20](=[CH:21][CH:22]=[CH:23][CH:24]=3)[CH2:19][O:18]2)=[CH:13][CH:12]=1

Komponenten

10

Edukt 6

HCID 222AmmoniaHCID 25517Ammonium ChlorideHCID 27779882-(3-Bromopropoxy)tetrahydro-2H-pyranHCID 5360545SodiumHCID 142302591-(4-Fluorophenyl)-1,3-dihydroisobenzofuranHCID 18522661Acetone cardice2×

Produkt 1

HCID 198835431-(4-fluorophenyl)-1,3-dihydro-1-[3-(tetrahydro-2H-pyran-2-yloxy)propyl]isobenzofuran

Reagenzien, Katalysatoren, Lösungsmittel 3

HCID 24380Iron chloride (FeCl3)KatalysatorHCID 962WaterLösungsmittelHCID 3283Diethyl EtherLösungsmittel2×

Versuchsvorschrift

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).

Aufarbeitung

  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

Quellen und Nachweise

ORD-Eintrag
ord-09d0a7ba29294be8a670de400e39ecad
Quelldatensatz
uspto-grants-1988_08
Patentnummer
US04766125

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