Morpholine → HCID 19899093, compound

HRID 1196671Notes

Reaction equation

HRID 1196671 reaction equation
O=[C:2]1[CH2:8][CH2:7][CH2:6][CH2:5][CH:4]([C:9]([O:11][CH3:12])=[O:10])[CH2:3]1.[NH:13]1CCOCC1.C(N(CC)CC)C.[Cl:26][C:27]1[CH:35]=[CH:34][C:30]([C:31](Cl)=[O:32])=[CH:29][CH:28]=1.Cl.C(N(CC)CC)C.Cl.NO>C1(C)C=CC=CC=1.C(O)C.C1(C)C=CC(S(O)(=O)=O)=CC=1.N1C=CC=CC=1.O>[Cl:26][C:27]1[CH:35]=[CH:34][C:30]([C:31]2[O:32][N:13]=[C:2]3[CH2:3][CH:4]([C:9]([O:11][CH3:12])=[O:10])[CH2:5][CH2:6][CH2:7][C:8]=23)=[CH:29][CH:28]=1

Participants

12

Reactant 6

HCID 8083MorpholineHCID 8471TriethylamineHCID 85014-Chlorobenzoyl chlorideHCID 11130Triethylamine hydrochlorideHCID 443297Hydroxyamine hydrochlorideHCID 13122878Methyl 3-oxocycloheptane-1-carboxylate

Product 1

HCID 19899093HCID 19899093, compoundYield 19.6%

Reagents, catalysts & solvents 5

HCID 6101p-Toluenesulfonic acidCatalystHCID 702EthanolSolventHCID 962WaterSolventHCID 1049PyridineSolventHCID 1140TolueneSolvent2×

Procedure

A solution of 3.4 g (0.02 mol) of methyl 3-oxocycloheptanecarboxylate, 1.91 g (0.022 mol) of morpholine and 0.005 g of p-toluenesulfonic acid in 30 ml of dry toluene was heated under reflux for 6 hours in a Dean-Stark apparatus until no additional water was collected. There were then added 2.02 g (0.02 mol) of triethylamine followed by a solution of 3.83 g (0.02.mol) of p-chlorobenzoyl chloride in 20 ml of toluene over a period of 10 minutes at 20° C. The mixture was heated at 60° C. for 6 hours, whereupon the precipitated triethylamine hydrochloride was removed from the cooled solution by filtration and washed with toluene. The combined toluene solutions were evaporated and 1.4 g (0.02 mol) of hydroxylamine hydrochloride dissolved in 10 ml of ethanol and 5 ml of pyridine were added. The mixture was heated under reflux for 2 hours. The solvent was removed by evaporation and an excess of 2N hydrochloric acid was added. The mixture was extracted twice with diethyl ether and the combined extracts were washed with 2N sodium carbonate solution and dried over magnesium sulfate. After evaporation, the resulting syrup was purified by column chromatography on silica gel using hexane/ethyl acetate (2:1) for the elution. There were obtained 1.2 g of methyl 3-(4-chlorophenyl)-5,6,7,8-tetrahydro-4H-cyclohept[c]isoxazole-7- -carboxylate of melting point 94°-95° C.

Workup

  1. customwas collected
  2. customwas removed from the cooled solution by filtration
  3. washwashed with toluene
  4. customThe combined toluene solutions were evaporated
  5. temperatureThe mixture was heated
  6. temperatureunder reflux for 2 hours
  7. customThe solvent was removed by evaporation
  8. additionan excess of 2N hydrochloric acid was added
  9. extractionThe mixture was extracted twice with diethyl ether
  10. washthe combined extracts were washed with 2N sodium carbonate solution
  11. dry with materialdried over magnesium sulfate
  12. customAfter evaporation
  13. customthe resulting syrup was purified by column chromatography on silica gel
  14. washfor the elution

Sources & evidence

ORD record
ord-ea2b5eed17f8458f90d3e802ad8809b8
Source dataset
uspto-grants-1992_05
Patent number
US05114960

Reaction notes

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