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

HRID 2085401Notes

Reaction equation

HRID 2085401 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]propylphthalimideYield 11.8%

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 at 95-100° C. for 12 h. About 80% of the solvent was evaporated under reduced pressure. The residue was diluted with ethyl acetate (200 mL) and washed with brine (3×100 mL) and dried (Na2SO4). The solvent was evaporated from the ethyl acetate solution and the residue was purified by column chromatography (1/1 hexane-ethyl acetate to 100% ethyl acetate), giving crude product (7.50 g, 88%). This crude product was crystallized from isopropanol, giving a white crystalline solid (4.50 g, 1st crop). This material was used in the next step. Concentration of the mother liquor and cooling gave the second crop of desired product (1.0 g). 1H NMR δ 1.43-1.52 (m, 2H), 1.67-1.75 (m, 2H), 1.80-1.96 (m, 4H), 2.33-2.46 (m, 3H), 2.94-2.99 (br d, 2H), 3.78 (t, J=7 Hz, 2H), 6.90-7.04 (m, 4H), 7.70-7.74 (m, 2H), 7.84-7.87 (m, 2H).

Workup

  1. customAbout 80% of the solvent was evaporated under 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. customThe solvent was evaporated from the ethyl acetate solution
  6. customthe residue was purified by column chromatography (1/1 hexane-ethyl acetate to 100% ethyl acetate)
  7. customgiving crude product (7.50 g, 88%)
  8. customThis crude product was crystallized from isopropanol
  9. customgiving a white crystalline solid (4.50 g, 1st crop)
  10. temperatureConcentration of the mother liquor and cooling

Sources & evidence

ORD record
ord-72e485f20b0345cc969056e77e1cd75f
Source dataset
uspto-grants-2004_04
Patent number
US06720324B2

Reaction notes

Loading…