Hydrochloric Acid → 4-(4-Fluorobenzoyl)-1-[2-(2-methoxyanilino)ethyl]piperidine

HRID 2461Notes

Reaction equation

HRID 2461 reaction equation
C(O[CH:4](OCC)[CH2:5][N:6]1[CH2:11][CH2:10][CH:9]([C:12](=[O:20])[C:13]2[CH:18]=[CH:17][C:16]([F:19])=[CH:15][CH:14]=2)[CH2:8][CH2:7]1)C.Cl.[CH3:25][O:26][C:27]1[C:28]([NH2:33])=[CH:29][CH:30]=[CH:31][CH:32]=1.C([BH3-])#N.[Na+].C(=O)([O-])[O-].[Na+].[Na+]>C1COCC1.CO>[F:19][C:16]1[CH:15]=[CH:14][C:13]([C:12]([CH:9]2[CH2:8][CH2:7][N:6]([CH2:5][CH2:4][NH:33][C:28]3[CH:29]=[CH:30][CH:31]=[CH:32][C:27]=3[O:26][CH3:25])[CH2:11][CH2:10]2)=[O:20])=[CH:18][CH:17]=1

Participants

8

Reactant 5

HCID 313Hydrochloric AcidHCID 70002-MethoxyanilineHCID 10340Sodium CarbonateHCID 5003444Sodium cyanoborohydrideHCID 196900081-(2,2-Diethoxyethyl)-4-(4-fluorobenzoyl)piperidine

Product 1

HCID 196900374-(4-Fluorobenzoyl)-1-[2-(2-methoxyanilino)ethyl]piperidineYield 66.2%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 8028TetrahydrofuranSolvent

Procedure

1-(2,2-Diethoxyethyl)-4-(4-fluorobenzoyl)piperidine (81 mg, 0.25 mmol) was dissolved in THF (3 ml) to which was subsequently added 10% hydrochloric acid (2 ml) at room temperature. After 1 hour of stirring at the same temperature, the solvent was removed by evaporation, and the resulting residue was subjected to azeotropic distillation using benzene (5 ml×4) to obtain an orange glutinous material. The thus obtained residue was dissolved in methanol (2 ml) to which were subsequently added o-anisidine (29 μl, 0.25 mmol) and sodium cyanoborohydride (11 mg, 0.166 mmol) at room temperature. After 2 hours of stirring at the same temperature, the reaction solution was mixed with saturated sodium carbonate aqueous solution (10 ml), extracted with ethyl acetate and then washed with water and saturated brine. The resulting organic layer was dried on anhydrous sodium carbonate, the solvent was removed by evaporation and then the resulting residue was purified by subjecting it to a silica gel column chromatography (ether:hexane=2:1-ether) to obtain 59 mg (66.2%) of the title compound in the form of colorless solid.

Workup

  1. customat room temperature
  2. customthe solvent was removed by evaporation
  3. distillationthe resulting residue was subjected to azeotropic distillation
  4. customto obtain an orange glutinous material
  5. customat room temperature
  6. stirringAfter 2 hours of stirring at the same temperature
  7. extractionextracted with ethyl acetate
  8. washwashed with water and saturated brine
  9. dry with materialThe resulting organic layer was dried on anhydrous sodium carbonate
  10. customthe solvent was removed by evaporation
  11. customthe resulting residue was purified

Sources & evidence

ORD record
ord-237b1973c5eb44b6bba25ecc54bfc269
Source dataset
uspto-grants-1998_03
Patent number
US05728835

Reaction notes

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