Potassium Carbonate → 1-[4-[3-[4-(6-Fluoro-1,2-benzisoxazol-3-yl)-1-piperidinyl] propoxy]-3-methoxyphenyl]propanone

HRID 1079505Notes

Reaction equation

HRID 1079505 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][CH2:25][CH2:26][O:27][C:28]1[CH:33]=[CH:32][C:31]([CH2:34][C:35](=[O:37])[CH3:36])=[CH:30][C:29]=1[O:38][CH3:39]>C(#N)C>[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][CH2:25][CH2:26][O:27][C:28]4[CH:33]=[CH:32][C:31]([CH2:34][C:35](=[O:37])[CH3:36])=[CH:30][C:29]=4[O:38][CH3:39])[CH2:13][CH2:14]3)=[N:7][O:8][C:4]=2[CH:3]=1

Participants

5

Reactant 3

HCID 11430Potassium CarbonateHCID 8494213-(4-Piperidyl)-6-fluoro-1,2-benzisoxazoleHCID 571029761-[4-(3-Bromopropoxy)-3-methoxyphenyl]propanone

Product 1

HCID 219600331-[4-[3-[4-(6-Fluoro-1,2-benzisoxazol-3-yl)-1-piperidinyl] propoxy]-3-methoxyphenyl]propanoneYield 31.8%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Procedure

A mixture of 6-fluoro-3-(4-piperidinyl)-1,2-benzisoxazole (2.8 g, 15.2 mmol), K2CO3 (3 g), 1-[4-(3-bromopropoxy)-3-methoxyphenyl]propanone (4.6 g, 18.2 mmol) in acetonitrile (100 ml) was heated at reflux for 2 hours. At the end of the reaction, the mixture was filtered and the solvent was concentrated and the residue was extracted into dichloromethane (300 ml). The dichloromethane was filtered and concentrated again. The crude material (6.4 g) was purified by flash chromatography over a silica gel column (SiO2, 50 g; eluted with dichloromethane, 700 ml; 1% methanol in dichloromethane, 1.4 l). The material thus purified (weight: 2.87 g, 51%) was recrystallized from ethanol (25 ml) to give 2.13 g of 1-[4-[3-[4-(6-fluoro-1,2-benzisoxazol-3-yl)-1-piperidinyl]propoxy]-3-methoxyphenyl]propanone as beige colored crystals, m.p.=118°-119° C.

Workup

  1. temperaturewas heated
  2. temperatureat reflux for 2 hours
  3. customAt the end of the reaction
  4. filtrationthe mixture was filtered
  5. concentrationthe solvent was concentrated
  6. extractionthe residue was extracted into dichloromethane (300 ml)
  7. filtrationThe dichloromethane was filtered
  8. concentrationconcentrated again
  9. customThe crude material (6.4 g) was purified by flash chromatography over a silica gel column (SiO2, 50 g; eluted with dichloromethane, 700 ml; 1% methanol in dichloromethane, 1.4 l)
  10. customThe material thus purified (weight: 2.87 g, 51%)
  11. customwas recrystallized from ethanol (25 ml)

Sources & evidence

ORD record
ord-429c58fbbce14079b1f2553a98fc7e9f
Source dataset
uspto-grants-1996_12
Patent number
US05580875

Reaction notes

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