Potassium Iodide → 1-{3-[4-(2-Methoxyphenyl)piperazin-1-yl]propyl}-4-(2,3,4,5,6-pentafluorophenoxy)piperidine

HRID 2072809Notes

Reaction equation

HRID 2072809 reaction equation
C(=O)([O-])[O-].[K+].[K+].[I-].[K+].[F:9][C:10]1[C:22]([F:23])=[C:21]([F:24])[C:20]([F:25])=[C:19]([F:26])[C:11]=1[O:12][CH:13]1[CH2:18][CH2:17][NH:16][CH2:15][CH2:14]1.Cl[CH2:28][CH2:29][CH2:30][N:31]1[CH2:36][CH2:35][N:34]([C:37]2[CH:42]=[CH:41][CH:40]=[CH:39][C:38]=2[O:43][CH3:44])[CH2:33][CH2:32]1>CN(C)C=O.O>[CH3:44][O:43][C:38]1[CH:39]=[CH:40][CH:41]=[CH:42][C:37]=1[N:34]1[CH2:33][CH2:32][N:31]([CH2:30][CH2:29][CH2:28][N:16]2[CH2:17][CH2:18][CH:13]([O:12][C:11]3[C:19]([F:26])=[C:20]([F:25])[C:21]([F:24])=[C:22]([F:23])[C:10]=3[F:9])[CH2:14][CH2:15]2)[CH2:36][CH2:35]1

Participants

7

Reactant 4

HCID 4875Potassium IodideHCID 11430Potassium CarbonateHCID 6226691-(3-Chloropropyl)-4-(2-methoxyphenyl)piperazineHCID 148370404-(2,3,4,5,6-Pentafluorophenoxy)piperidine

Product 1

HCID 148370561-{3-[4-(2-Methoxyphenyl)piperazin-1-yl]propyl}-4-(2,3,4,5,6-pentafluorophenoxy)piperidineYield 51.4%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent2×

Conditions

Temperature
75 °C

Procedure

A mixture of 10 g of potassium carbonate, 0.18 g of potassium iodide, 4.0 g of 4-(2,3,4,5,6-pentafluorophenoxy)piperidine and 50 ml of dimethylformamide was treated with a solution of 4.56 g of 1-(3-chloropropyl)-4-(2-methoxyphenyl)piperazine in 25 ml dimethylformamide and stirred for seven hours at 75° C. After cooling to room temperature, the reaction mixture was poured into water and extracted with ethyl acetate. The organic layer was washed with water followed by a saturated sodium chloride solution and dried over anhydrous magnesium sulfate. After filtering, evaporation afforded a residue which was purified by means of high pressure liquid chromatography (silica gel; elution with 7.5% methanol/dichloromethane). Evaporation of the appropriate fractions afforded 3.84 g of 1-{3-[4-(2-methoxyphenyl)piperazin-1-yl]propyl}-4-(2,3,4,5,6-pentaflurophenoxy)piperidine as an oil. The oil was dissolved in isopropanol and acidified to pH 1 with etheral hydrogen chloride to precipitate the corresponding dihydrochloride salt. Recrystallization from isopropanol afforded 3.34 g (44.6%) of 1-{3-[4-(2-methoxyphenyl)piperazin-1-yl]propyl}-4-(2,3,4,5,6-pentaflurophenoxy)piperidine hydrochloride, m.p. 261°-263° C.

Workup

  1. temperatureAfter cooling to room temperature
  2. extractionextracted with ethyl acetate
  3. washThe organic layer was washed with water
  4. dry with materialdried over anhydrous magnesium sulfate
  5. filtrationAfter filtering
  6. customevaporation
  7. customafforded a residue which
  8. customwas purified by means of high pressure liquid chromatography (silica gel; elution with 7.5% methanol/dichloromethane)
  9. customEvaporation of the appropriate fractions

Sources & evidence

ORD record
ord-e93c31e3d8e346169d7d2f4657f0e341
Source dataset
uspto-grants-1990_04
Patent number
US04914204

Reaction notes

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