Potassium Carbonate → 4-Cyano-1-[3-(6-fluoro-1,2-benzisoxazol-3-yl)propyl]-4-phenylpiperidine hydrochloride

HRID 280896

Reaction equation

HRID 280896 reaction equation
Cl.[C:2]([C:4]1([C:10]2[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=2)[CH2:9][CH2:8][NH:7][CH2:6][CH2:5]1)#[N:3].[Cl:16][CH2:17][CH2:18][CH2:19][C:20]1[C:24]2[CH:25]=[CH:26][C:27]([F:29])=[CH:28][C:23]=2[O:22][N:21]=1.C(=O)([O-])[O-].[K+].[K+]>[I-].[K+].CN(C)C=O>[ClH:16].[C:2]([C:4]1([C:10]2[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=2)[CH2:5][CH2:6][N:7]([CH2:17][CH2:18][CH2:19][C:20]2[C:24]3[CH:25]=[CH:26][C:27]([F:29])=[CH:28][C:23]=3[O:22][N:21]=2)[CH2:8][CH2:9]1)#[N:3]

Participants

6

Reactant 3

HCID 11430Potassium CarbonateHCID 30849734-Phenylpiperidine-4-carbonitrile hydrochlorideHCID 109108803-(3-Chloropropyl)-6-fluorobenzo[d]isoxazole

Product 1

HCID 133198724-Cyano-1-[3-(6-fluoro-1,2-benzisoxazol-3-yl)propyl]-4-phenylpiperidine hydrochlorideYield 30.4%

Reagents, catalysts & solvents 2

HCID 4875Potassium IodideCatalystHCID 6228DimethylformamideSolvent

Conditions

Temperature
90 °C

Procedure

To 50 ml of dimethylformamide was added 4.4 g of 4-cyano-4-phenylpiperidine hydrochloride, 6.4 g of 3-(3-chloropropyl)-6-fluoro-1,2-benzisoxazole, 10 g of milled potassium carbonate, and 0.01 g of potassium iodide. After stirring at 90° C. for three hrs, the mixture was cooled, filtered, and the filtrate was evaporated to an oil. The oil was stirred with 100 ml of water for ten mins and then extracted with ether. The ether solution was washed with water (2x), saturated sodium chloride solution and dried over anhydrous magnesium sulfate. After filtering, the solvent was evaporated. The residue was filtered through a silica gel column with tetrahydrofuran. The eluant was evaporated to an oil. The oil was dissolved in ether and treated with ethereal hydrogen chloride to give 2.4 g (29%) of product, mp 235° C. (dec). Recrystallization from ethyl acetate/methanol gave the analytical sample, mp 239° C.

Workup

  1. temperaturethe mixture was cooled
  2. filtrationfiltered
  3. customthe filtrate was evaporated to an oil
  4. stirringThe oil was stirred with 100 ml of water for ten mins
  5. extractionextracted with ether
  6. washThe ether solution was washed with water (2x), saturated sodium chloride solution
  7. dry with materialdried over anhydrous magnesium sulfate
  8. filtrationAfter filtering
  9. customthe solvent was evaporated
  10. filtrationThe residue was filtered through a silica gel column with tetrahydrofuran
  11. customThe eluant was evaporated to an oil
  12. dissolutionThe oil was dissolved in ether
  13. additiontreated with ethereal hydrogen chloride

Sources & evidence

ORD record
ord-0b413f610e0e4919aca5324749640a11
Source dataset
uspto-grants-1986_05
Patent number
US04591586

Linked notes

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