Ethyl Acetate → HCID 19786595, compound

HRID 1196601Notes

Reaction equation

HRID 1196601 reaction equation
Cl.[CH3:2][N:3]([CH2:5][CH:6]1[C:21](=[O:22])[C:10]2[C:11]([C:14]3[CH:19]=[CH:18][CH:17]=[CH:16][C:15]=3[F:20])=[N:12][O:13][C:9]=2[CH2:8][CH2:7]1)[CH3:4].Cl.[F:24][C:25]1[CH:38]=[CH:37][C:28]([C:29]([CH:31]2[CH2:36]CNC[CH2:32]2)=[O:30])=[CH:27][CH:26]=1.C(=O)([O-])[O-].[K+].[K+].C(OCC)(=O)C>O>[F:24][C:25]1[CH:26]=[CH:27][C:28]([C:29]([CH:31]2[CH2:32][CH2:2][N:3]([CH2:5][CH:6]3[C:21](=[O:22])[C:10]4[C:11]([C:14]5[CH:19]=[CH:18][CH:17]=[CH:16][C:15]=5[F:20])=[N:12][O:13][C:9]=4[CH2:8][CH2:7]3)[CH2:4][CH2:36]2)=[O:30])=[CH:37][CH:38]=1

Participants

6

Reactant 4

HCID 8857Ethyl AcetateHCID 11430Potassium CarbonateHCID 3084438p-Fluorophenyl 4-piperidyl ketone hydrochlorideHCID 19786590HCID 19786590, compound

Product 1

HCID 19786595HCID 19786595, compoundYield 46.5%

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Procedure

To a solution consisting of 6,7-dihydro-5-dimethylaminomethyl-3-(2-fluorophenyl)-1,2-benzisoxazol-4(5H)-one hydrochloride (1.86 g) in distilled water (18.5 ml) was added 4-(4-fluorobenzoyl)piperidine hydrochloride (2.78 g) and potassium carbonate (0.80 g). The reaction mixture was heated at reflux for 3 hours. Upon cooling to room temperature, ethyl acetate was added and the layers were separated. The aqueous phase was extracted twice with ethyl acetate. The combined organic layers were washed with brine and dried (MgSO4). Filtration and concentration gave the crude product. Purification via flash column chromatography (silica gel, 40% ethyl acetate/hexane) PG,54 afforded 1.20 g of 6,7-dihydro-5-(4-(4-fluorobenzoyl)-1-piperidinyl)methyl-3-(2-fluorophenyl)-1,2-benzisoxazol-4(5H)-one. The compound was flushed through alumina with dichloromethane to give an oil which solidified on standing. The product was then recrystallized from ether/hexane, m.p. 99°-102° C.

Workup

  1. temperatureThe reaction mixture was heated
  2. temperatureat reflux for 3 hours
  3. customthe layers were separated
  4. extractionThe aqueous phase was extracted twice with ethyl acetate
  5. washThe combined organic layers were washed with brine
  6. dry with materialdried (MgSO4)
  7. filtrationFiltration and concentration
  8. customgave the crude product
  9. customPurification via flash column chromatography (silica gel, 40% ethyl acetate/hexane) PG,54

Sources & evidence

ORD record
ord-77c2f8d927f9449986da85d3cb982b14
Source dataset
uspto-grants-1992_05
Patent number
US05114936

Reaction notes

Loading…