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 2229709Notes

Reaction equation

HRID 2229709 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+].[ClH:28].[C:29](#[N:31])[CH3:30]>C(O)C>[ClH:28].[ClH:28].[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:31]4[CH2:11][C:12]5[C:30](=[CH:5][CH:6]=[CH:7][CH:8]=5)[CH2:29]4)[CH2:3][CH2:2]3)=[N:9][O:10][C:11]=2[CH:16]=1

Participants

6

Reactant 4

HCID 313Hydrochloric AcidHCID 6342AcetonitrileHCID 11430Potassium CarbonateHCID 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 (2.24g, 7.6 mmol), K2CO3 (1.61 g, 11.7 mmol) in acetonitrile (100 ml) was added αα′-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-1aa8c60436a94c6486c6ce5650e6639c
Source dataset
uspto-grants-2002_07
Patent number
US06420390B1

Reaction notes

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