Potassium Carbonate → 3-[4-(4-Fluorophenyl)piperidin-1-yl]propylphthalimide

HRID 2269214Notes

Reaction equation

HRID 2269214 reaction equation
Cl.[F:2][C:3]1[CH:8]=[CH:7][C:6]([CH:9]2[CH2:14][CH2:13][NH:12][CH2:11][CH2:10]2)=[CH:5][CH:4]=1.Br[CH2:16][CH2:17][CH2:18][C:19]1[CH:29]=[CH:28][CH:27]=[C:21]2[C:22]([NH:24][C:25](=[O:26])[C:20]=12)=[O:23].C(=O)([O-])[O-].[K+].[K+]>CN(C=O)C>[F:2][C:3]1[CH:8]=[CH:7][C:6]([CH:9]2[CH2:10][CH2:11][N:12]([CH2:16][CH2:17][CH2:18][C:19]3[CH:29]=[CH:28][CH:27]=[C:21]4[C:22]([NH:24][C:25](=[O:26])[C:20]=34)=[O:23])[CH2:13][CH2:14]2)=[CH:5][CH:4]=1

Participants

5

Reactant 3

HCID 11430Potassium CarbonateHCID 218981684-(4-Fluoro-phenyl)-piperidine hydrochlorideHCID 21958088Bromopropylphthalimide

Product 1

HCID 227294733-[4-(4-Fluorophenyl)piperidin-1-yl]propylphthalimide

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
97.5 °C

Procedure

A mixture of 4-(4-fluorophenyl)piperidine hydrochloride (5.08 g, 23.2 mmol), 3-bromopropylphthalimide (6.22 g, 23.2 mmol), and potassium carbonate (15 g) in DMF (100 mL) was stirred and heated at 95-100° C. for 12 h. About 80% of the solvent was evaporated at reduced pressure, the residue was diluted with ethyl acetate (200 mL) and washed with brine (3×100 mL) and dried (Na2SO4). Solvent was evaporated and the residue was purified by column chromatography on silica gel using 1/1 hexane-ethyl acetate to 100% ethyl acetate as eluent. This product was crystallized from isopropanol to give a white crystalline solid; m.p. 80-81° C. This material was used in the next step. Concentration of the mother liquor and cooling gave the second crop.

Workup

  1. customAbout 80% of the solvent was evaporated at reduced pressure
  2. additionthe residue was diluted with ethyl acetate (200 mL)
  3. washwashed with brine (3×100 mL)
  4. dry with materialdried (Na2SO4)
  5. customSolvent was evaporated
  6. customthe residue was purified by column chromatography on silica gel using 1/1 hexane-ethyl acetate to 100% ethyl acetate as eluent
  7. customThis product was crystallized from isopropanol
  8. customto give a white crystalline solid
  9. temperatureConcentration of the mother liquor and cooling
  10. customgave the second crop

Sources & evidence

ORD record
ord-d374422b13d040e78d34cf9883fbbf9c
Source dataset
uspto-grants-2001_12
Patent number
US06329393B1

Reaction notes

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