Potassium Carbonate → 4-(6-Fluoro-1,2-benzisoxazol-yl)-1-[3-(2,3-dihydro-1H-isoindol-2-yl)propyl]piperidine Difumarate

HRID 55688Notes

Reaction equation

HRID 55688 reaction equation
[F:1][C:2]1[CH:20]=[CH:19][C:5]2[C:6]([CH:9]3[CH2:14][CH2:13][N:12]([CH2:15][CH2:16][CH2:17][NH2:18])[CH2:11][CH2:10]3)=[N:7][O:8][C:4]=2[CH:3]=1.C([O-])([O-])=O.[K+].[K+].Br[CH2:28][C:29]1[C:30]([CH2:35]Br)=[CH:31][CH:32]=[CH:33][CH:34]=1.[C:37]([OH:44])(=[O:43])/[CH:38]=[CH:39]/[C:40]([OH:42])=[O:41]>C(#N)C.C(O)C>[C:37]([OH:44])(=[O:43])/[CH:38]=[CH:39]/[C:40]([OH:42])=[O:41].[C:37]([OH:44])(=[O:43])/[CH:38]=[CH:39]/[C:40]([OH:42])=[O:41].[F:1][C:2]1[CH:20]=[CH:19][C:5]2[C:6]([CH:9]3[CH2:14][CH2:13][N:12]([CH2:15][CH2:16][CH2:17][N:18]4[CH2:35][C:30]5[C:29](=[CH:34][CH:33]=[CH:32][CH:31]=5)[CH2:28]4)[CH2:11][CH2:10]3)=[N:7][O:8][C:4]=2[CH:3]=1

Participants

7

Reactant 4

HCID 11430Potassium CarbonateHCID 66665o-Bis(bromomethyl)benzeneHCID 444972Fumaric AcidHCID 146998441-(Aminopropyl)-4-(6-fluoro-1,2-benzisoxazol-3-yl)piperidine

Product 1

HCID 670711894-(6-Fluoro-1,2-benzisoxazol-yl)-1-[3-(2,3-dihydro-1H-isoindol-2-yl)propyl]piperidine Difumarate

Reagents, catalysts & solvents 2

HCID 702EthanolSolvent2×HCID 6342AcetonitrileSolvent

Procedure

A stirred mixture of 3-[4-(6-fluoro-1,2-benzisoxazol-3-yl)-1-piperidinyl]propyl amine (3.46 g, 12.5 mmol), K2CO3 (4 g, 29 mmol) and α,α'-dibromo-o-xylene (3.3 g, 12.5 mmol) in acetonitrile (300 ml) was heated at reflux for 3.5 hours. The mixture was cooled and the insolubles were filtered. The dark red solution was concentrated down to a dark oil. This oil was purified by flash chromatography over a silica gel column (SiO2, 45 g; eluded with dichloromethane and MeOH in dichloromethane). The product thus obtained weighed 1.95 g as an oil. This oil was dissolved in ethanol and was treated with a solution of fumaric acid (600 mg) in ethanol. The resulting crystals were collected as an off white solid and weighed 1.44 gm, m.p. 206°-209° C.

Workup

  1. temperaturewas heated
  2. temperatureat reflux for 3.5 hours
  3. temperatureThe mixture was cooled
  4. filtrationthe insolubles were filtered
  5. concentrationThe dark red solution was concentrated down to a dark oil
  6. customThis oil was purified by flash chromatography over a silica gel column (SiO2, 45 g; eluded with dichloromethane and MeOH in dichloromethane)
  7. customThe product thus obtained
  8. customThe resulting crystals were collected as an off white solid

Sources & evidence

ORD record
ord-86badd009b5d42ae8e57e8895cfa6d52
Source dataset
uspto-grants-1997_04
Patent number
US05624927

Reaction notes

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