Hydrochloric Acid → N-[3-[4-(6-Fluoro-1,2-benzisoxazol-3-yl)-1-piperidinyl]-2-hydroxy-1-propyl]2,3-dihydro-1H-isoindole dihydrochloride

HRID 55689Notes

Reaction equation

HRID 55689 reaction equation
N[CH:2]1[CH:7]([C:8]2[C:12]3[CH:13]=[CH:14][C:15]([F:17])=[CH:16][C:11]=3[O:10][N:9]=2)[CH2:6][CH2:5][N:4]([CH2:18][CH:19]([OH:21])[CH3:20])[CH2:3]1.C([O-])([O-])=O.[K+].[K+].Br[CH2:29][C:30]1[C:31]([CH2:36]Br)=[CH:32][CH:33]=[CH:34][CH:35]=1.[ClH:38].C(#[N:41])C>C(O)C>[ClH:38].[ClH:38].[F:17][C:15]1[CH:14]=[CH:13][C:12]2[C:8]([CH:7]3[CH2:6][CH2:5][N:4]([CH2:18][CH:19]([OH:21])[CH2:20][N:41]4[CH2:36][C:31]5[C:30](=[CH:35][CH:34]=[CH:33][CH:32]=5)[CH2:29]4)[CH2:3][CH2:2]3)=[N:9][O:10][C:11]=2[CH:16]=1

Participants

7

Reactant 5

HCID 313Hydrochloric AcidHCID 6342AcetonitrileHCID 11430Potassium CarbonateHCID 66665o-Bis(bromomethyl)benzeneHCID 867497613-Amino-2-hydroxypropyl-4-(6-fluoro-1,2-benzisoxazol-yl)piperidine

Product 1

HCID 18467298N-[3-[4-(6-Fluoro-1,2-benzisoxazol-3-yl)-1-piperidinyl]-2-hydroxy-1-propyl]2,3-dihydro-1H-isoindole dihydrochloride

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent2×

Procedure

To a stirred mixture of 1-(3-amino-2-hydroxypropyl-4-(6-fluoro-1,2-benzisoxazol-3-yl)piperidine (2.24 g, 7.6 mmol), K2CO3 (1.61 g, 11.7 mmol) in acetonitrile (100 ml) was added α,α'-dibromo-o-xylene (1.54 g, 6.1 mmol). The mixture was heated at reflux for 4 hours then cooled. The insolubles were filtered. The dark red solution was concentrated down. The residue was purified by flash chromatography over s silica gel column (SiO2, 30 g; eluted with 1% CH3OH in dichloromethane). The product so obtained weighed 940 mg as an oil. This oil was dissolved in ethanol and was treated with a solution of HCl in ethanol (188 mg of AcCl in ethanol). The dark solids were collected and recrystallized again in ethanol to yield off-white crystals (1.01 g), m.p. 240°-243° C.

Workup

  1. temperatureThe mixture was heated
  2. temperatureat reflux for 4 hours
  3. temperaturethen cooled
  4. filtrationThe insolubles were filtered
  5. concentrationThe dark red solution was concentrated down
  6. customThe residue was purified by flash chromatography over s silica gel column (SiO2, 30 g; eluted with 1% CH3OH in dichloromethane)
  7. customThe product so obtained
  8. customThe dark solids were collected
  9. customrecrystallized again in ethanol

Sources & evidence

ORD record
ord-386caf012bb349cda9ab972565b08f71
Source dataset
uspto-grants-1997_04
Patent number
US05624927

Reaction notes

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