Potassium Iodide → 1-[-(6-Fluoro-1,2-benzisoxazol-3-yl)propyl]-4-(2,3,4,5,6-pentafluorophenoxy)piperidine

HRID 2072806Notes

Reaction equation

HRID 2072806 reaction equation
C(=O)(O)[O-].[Na+].[I-].[K+].[F:8][C:9]1[C:21]([F:22])=[C:20]([F:23])[C:19]([F:24])=[C:18]([F:25])[C:10]=1[O:11][CH:12]1[CH2:17][CH2:16][NH:15][CH2:14][CH2:13]1.Cl[CH2:27][CH2:28][CH2:29][C:30]1[C:34]2[CH:35]=[CH:36][C:37]([F:39])=[CH:38][C:33]=2[O:32][N:31]=1>CN(C)C=O.O>[F:39][C:37]1[CH:36]=[CH:35][C:34]2[C:30]([CH2:29][CH2:28][CH2:27][N:15]3[CH2:16][CH2:17][CH:12]([O:11][C:10]4[C:18]([F:25])=[C:19]([F:24])[C:20]([F:23])=[C:21]([F:22])[C:9]=4[F:8])[CH2:13][CH2:14]3)=[N:31][O:32][C:33]=2[CH:38]=1

Participants

7

Reactant 4

HCID 4875Potassium IodideHCID 516892Sodium BicarbonateHCID 109108803-(3-Chloropropyl)-6-fluorobenzo[d]isoxazoleHCID 148370404-(2,3,4,5,6-Pentafluorophenoxy)piperidine

Product 1

HCID 148370511-[-(6-Fluoro-1,2-benzisoxazol-3-yl)propyl]-4-(2,3,4,5,6-pentafluorophenoxy)piperidineYield 38.3%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent2×

Conditions

Temperature
68 °C

Procedure

A mixture of 10 g of sodium bicarbonate, and 0.10 g of potassium iodide, 4.13 g of 4-(2,3,4,5,6-pentafluorophenoxy)piperidine and 75 ml of dimethylformamide was treated with a solution of 3.41 g of 3-(3-chloropropyl)-6-fluoro-1,2-benzisoxazole in 25 ml dimethylformamide and stirred at 68° C. for 5.5 hours. The mixture was then cooled, poured into water, and then 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 of the volatiles afforded a residue which was purified by means of high pressure liquid chromatography (silica gel; elution with ethyl acetate) to yield 2.63 g of 1-[-(6-fluoro-1,2-benzisoxazol-3-yl)propyl]-4-(2,3,4,5,6-pentafluorophenoxy)piperidine as an oil. The oil was dissolved in diethyl ether and the solution acidified to pH 1 with etheral hydrogen chloride to precipitate the corresponding hydrochloride salt. Recrystallization from isopropanol afforded 1.80 g (15.4%) of 1-[ -(6-fluoro-1,2-benzisoxazol-3-yl)propyl]-4-(2,3,4,5,6-pentafluorophenoxy)piperidine hydrochloride, m.p. 187°-189° C.

Workup

  1. temperatureThe mixture was then cooled
  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 of the volatiles
  7. customafforded a residue which
  8. customwas purified by means of high pressure liquid chromatography (silica gel; elution with ethyl acetate)

Sources & evidence

ORD record
ord-f25b60fd8e4248cf8ce5ae88a4e9e98e
Source dataset
uspto-grants-1990_04
Patent number
US04914204

Reaction notes

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