Potassium Carbonate → 1-[2-[3-[4-(6-Fluoro-1,2-benzisoxazol-3-yl)1-piperidinyl]propoxy]-5-methylphenyl]ethanone

HRID 744201Notes

Reaction equation

HRID 744201 reaction equation
Cl.[F:2][C:3]1[CH:17]=[CH:16][C:6]2[C:7]([CH:10]3[CH2:15][CH2:14][NH:13][CH2:12][CH2:11]3)=[N:8][O:9][C:5]=2[CH:4]=1.C([O-])([O-])=O.[K+].[K+].Br[CH2:25][CH2:26][CH2:27][O:28][C:29]1[CH:34]=[CH:33][C:32]([CH3:35])=[CH:31][C:30]=1[C:36](=[O:38])[CH3:37]>CN(C)C=O.C(#N)C>[F:2][C:3]1[CH:17]=[CH:16][C:6]2[C:7]([CH:10]3[CH2:11][CH2:12][N:13]([CH2:25][CH2:26][CH2:27][O:28][C:29]4[CH:34]=[CH:33][C:32]([CH3:35])=[CH:31][C:30]=4[C:36](=[O:38])[CH3:37])[CH2:14][CH2:15]3)=[N:8][O:9][C:5]=2[CH:4]=1

Participants

6

Reactant 3

HCID 11430Potassium CarbonateHCID 104232991-[2-(3-Bromopropoxy)-5-methylphenyl]ethanoneHCID 11334359R-56109 hydrochloride

Product 1

HCID 104766811-[2-[3-[4-(6-Fluoro-1,2-benzisoxazol-3-yl)1-piperidinyl]propoxy]-5-methylphenyl]ethanoneYield 46.2%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 6342AcetonitrileSolvent

Conditions

Temperature
95 °C

Procedure

A mixture of 6-fluoro-3-(4-piperidinyl)-1,2-benzisoxazole hydrochloride (2.87 g, 11.23 mmol), K2CO3 (2.5 g), 1-[2-(3-bromopropoxy)-5-methylphenyl]ethanone (3.74 g, 13.8 mmol) in dimethylformamide (10 ml) and acetonitrile (50 ml) was heated at 95° C. for 6 hours. At the end of the reaction, the solvent was concentrated and the mixture was extracted into dichloromethane (300 ml). The organic solution was washed with water and brine, dried over MgSO4, then concentrated down to a crude oil. The purification was done by flash chromatography over a silica gel column (SiO2, 60 g, eluted with 1% CH3OH:dichloromethane: 1.2 l; 3% CH3OH:dichloromethane: 600 ml). The material thus obtained was crystallized from a small volume of ether and hexane to provide 2.13 g (46%) of off-white 1-[2-[3-[4-(6-fluoro-1,2-benzisoxazol-3-yl)-1-piperidinyl]propoxy]-5-methylphenyl]ethanone, m.p.=92°-93° C.

Workup

  1. customAt the end of the reaction
  2. concentrationthe solvent was concentrated
  3. extractionthe mixture was extracted into dichloromethane (300 ml)
  4. washThe organic solution was washed with water and brine
  5. dry with materialdried over MgSO4
  6. concentrationconcentrated down to a crude oil
  7. customThe purification
  8. washwas done by flash chromatography over a silica gel column (SiO2, 60 g, eluted with 1% CH3OH:dichloromethane: 1.2 l; 3% CH3OH:dichloromethane: 600 ml)
  9. customThe material thus obtained
  10. customwas crystallized from a small volume of ether and hexane

Sources & evidence

ORD record
ord-0d1bd60be0ee4a44866d6a3cd86c08d9
Source dataset
uspto-grants-1996_09
Patent number
US05559116

Reaction notes

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