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

HRID 1450774Notes

Reaction equation

HRID 1450774 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:36]=[CH:35][C:31]([C:32]([NH2:34])=[O:33])=[CH:30][C:29]=1[O:37][CH3:38]>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:36]=[CH:35][C:31]([C:32]([NH2:34])=[O:33])=[CH:30][C:29]=4[O:37][CH3:38])[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 101081354-(3-Bromopropoxy)3-methoxybenzamide

Product 1

HCID 104552114-[3-[4-(6-Fluoro-1,2-benzisoxazol-3-yl)1-piperidinyl]propoxy]-3-methoxybenzamideYield 64.3%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Procedure

A mixture of 6-fluoro-3-(4-piperidinyl)-1,2-benzisoxazole (2.2 g, 10.0 mmol), K2CO3 (2.0 g) and 4-(3-bromopropoxy)-3-methoxybenzamide (2.32 g, 8.0 mmol) in acetonitrile (80 ml) was heated at reflux for 5 hours. At the end of the reaction the solvent was evaporated. The residue was extracted into dichloromethane. The inorganic insolubles were filtered off. The dichloromethane was concentrated again. The crude residue was.purified by flash chromatography over a silica gel column (55 g, SiO2 ; eluted with 1% methanol in dichloromethane, 1 l; 2% methanol in dichloromethane, 1 l). The material thus obtained weighed 2.93 g (84%) as white crystals. Recrystallization from hot ethanol (60 ml) gave 2.2 g of 4-[3-[4-(6-fluoro-1,2-benzisoxazol-3-yl)-1-piperidinyl]propoxy]-3-methoxybenzamide as white crystals, m.p. =163°-164° C.

Workup

  1. temperaturewas heated
  2. temperatureat reflux for 5 hours
  3. customAt the end of the reaction the solvent
  4. customwas evaporated
  5. extractionThe residue was extracted into dichloromethane
  6. filtrationThe inorganic insolubles were filtered off
  7. concentrationThe dichloromethane was concentrated again
  8. washThe crude residue was.purified by flash chromatography over a silica gel column (55 g, SiO2 ; eluted with 1% methanol in dichloromethane, 1 l; 2% methanol in dichloromethane, 1 l)
  9. customThe material thus obtained
  10. customRecrystallization from hot ethanol (60 ml)

Sources & evidence

ORD record
ord-d30b52b9fb524449a1907dc3c9063537
Source dataset
uspto-grants-1997_02
Patent number
US05602159

Reaction notes

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