Hydrochloric Acid → 4-(6-Fluoro-1,2-benzisoxazol-3-yl)-1-piperidinyl-2-propanone hydrochloride

HRID 55672Notes

Reaction equation

HRID 55672 reaction equation
[F:1][C:2]1[CH:16]=[CH:15][C:5]2[C:6]([CH:9]3[CH2:14][CH2:13][NH:12][CH2:11][CH2:10]3)=[N:7][O:8][C:4]=2[CH:3]=1.C([O-])([O-])=O.[K+].[K+].Br[CH2:24][C:25](OC)([O:27]C)[CH3:26].[ClH:31]>C(#N)C.CCOCC.C(O)C>[ClH:31].[F:1][C:2]1[CH:16]=[CH:15][C:5]2[C:6]([CH:9]3[CH2:10][CH2:11][N:12]([CH2:24][C:25](=[O:27])[CH3:26])[CH2:13][CH2:14]3)=[N:7][O:8][C:4]=2[CH:3]=1

Participants

8

Reactant 4

HCID 313Hydrochloric AcidHCID 11430Potassium CarbonateHCID 671751-Bromo-2,2-dimethoxypropane2×HCID 8494213-(4-Piperidyl)-6-fluoro-1,2-benzisoxazole

Product 1

HCID 184673524-(6-Fluoro-1,2-benzisoxazol-3-yl)-1-piperidinyl-2-propanone hydrochloride

Reagents, catalysts & solvents 3

HCID 702EthanolSolventHCID 3283Diethyl EtherSolventHCID 6342AcetonitrileSolvent

Procedure

A mixture of 4-(6-fluoro-1,2-benzisoxazol-3-yl)piperidine (7.45 g, 33.4 mmol), K2CO3 (5.5 g) and bromo-2,2-dimethoxypropane (6.84 g, 37.6 mmol) in acetonitrile (200 ml) was heated and stirred at reflux for 4 hours. An additional charge of bromo-2,2-dimethoxypropane (5.1 g, 28 mmol) was added and the mixture was refluxed overnight. After being cooled to room temperature, the mixture was filtered, and the solvent was removed on a rotary evaporator. The residue was purified by flash chromatography over a silica gel column (SiO2, 100 g; eluted with dichloromethane, DCM, and 1% CH3OH in DCM). The oil product thus obtained weighed 2.2 g (24%). The oil product was dissolved into ethanol (10 ml) then was treated with HCl in ether solution (1M, 9 ml) at room temperature. The crystals were collected, 2.08 g, m.p.=220°-223° C. dec.

Workup

  1. temperaturewas heated
  2. temperatureat reflux for 4 hours
  3. additionwas added
  4. temperaturethe mixture was refluxed overnight
  5. filtrationthe mixture was filtered
  6. customthe solvent was removed on a rotary evaporator
  7. customThe residue was purified by flash chromatography over a silica gel column (SiO2, 100 g; eluted with dichloromethane, DCM, and 1% CH3OH in DCM)
  8. customThe oil product thus obtained
  9. customThe crystals were collected

Sources & evidence

ORD record
ord-f98dd732eb2d4e928b1f617abad1f0b0
Source dataset
uspto-grants-1997_04
Patent number
US05624927

Reaction notes

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