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

HRID 2211489Notes

Reaction equation

HRID 2211489 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 mmoles), K2CO3 (2.0 g) and 4-(3-bromopropoxy)-3-methoxybenzamide (2.32 g, 8.0 mmoles) in acetonitrile i80 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 weighted 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-methoxy- benzamide 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. customThe 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. customRecrystallization from hot ethanol (60 ml)

Sources & evidence

ORD record
ord-e3bc531127ae43f9ac0b92444ac4a00c
Source dataset
uspto-grants-2006_09
Patent number
USRE039265E1

Reaction notes

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