Potassium Carbonate → N-[3-[3-[4(6-fluoro-1,2-benzisoxazol-3-yl) 1-piperidinyl]propoxy]phenyl]acetamide hemifumarate

HRID 1601523Notes

Reaction equation

HRID 1601523 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+].[C:23]([NH:26][C:27]1[CH:28]=[C:29]([CH:35]=[CH:36][CH:37]=1)[O:30][CH2:31][CH2:32][CH2:33]Br)(=[O:25])[CH3:24].[C:38]([OH:45])(=[O:44])/[CH:39]=[CH:40]/[C:41]([OH:43])=[O:42]>C(#N)C.C(O)C>[C:38]([OH:45])(=[O:44])/[CH:39]=[CH:40]/[C:41]([OH:43])=[O:42].[F:1][C:2]1[CH:16]=[CH:15][C:5]2[C:6]([CH:9]3[CH2:10][CH2:11][N:12]([CH2:33][CH2:32][CH2:31][O:30][C:29]4[CH:28]=[C:27]([NH:26][C:23](=[O:25])[CH3:24])[CH:37]=[CH:36][CH:35]=4)[CH2:13][CH2:14]3)=[N:7][O:8][C:4]=2[CH:3]=1.[F:1][C:2]1[CH:16]=[CH:15][C:5]2[C:6]([CH:9]3[CH2:10][CH2:11][N:12]([CH2:33][CH2:32][CH2:31][O:30][C:29]4[CH:28]=[C:27]([NH:26][C:23](=[O:25])[CH3:24])[CH:37]=[CH:36][CH:35]=4)[CH2:13][CH2:14]3)=[N:7][O:8][C:4]=2[CH:3]=1

Participants

7

Reactant 4

HCID 11430Potassium CarbonateHCID 444972Fumaric AcidHCID 8494213-(4-Piperidyl)-6-fluoro-1,2-benzisoxazoleHCID 6420330N-[3-(3-Bromo-propoxy)-phenyl]-acetamide

Product 1

HCID 131719501N-[3-[3-[4(6-fluoro-1,2-benzisoxazol-3-yl) 1-piperidinyl]propoxy]phenyl]acetamide hemifumarate

Reagents, catalysts & solvents 2

HCID 702EthanolSolvent2×HCID 6342AcetonitrileSolvent

Procedure

A stirred mixture of 6fluoro-3-(4-piperidinyl)-1,2-benzisoxazole(9.25 g, 42 mmol). K2CO3 (8 g, 58 mmol) and 3-(3-acetamidophenoxy)propyl bromide (11.4 g, 42 mmol) in acetonitrile (350 ml) was heated at reflux for 3 hours. At the end of the reaction, the reaction was cooled, filtered and the solids washed with dichloromethane (100 ml). the organic solvent was removed on a rotary evaporator to leave a crude oil (18 g). Purification was by flash chromatography on a silica gel column. The product thus purified was an oil, 12.2 g, 70%. Analytically pure sample was prepared by dissolving 3 g of free base in ethanol and treating with fumaric acid solution in ethanol (850 mg:5 ml). The N-[3-[3-[4-(6-fluoro-1,2-benzisoxazol-3-yl)-1-piperidinyl]propoxy]phenyl]acetamide hemifumarate crystals obtained weighed 2.73 g, m.p.=184-186° C. Calculated for C23H26FN 3O2.0.5C4H4O4 : 63.95% C 6.01% H 8.94% N; Found: 63.47% C 5.94% H 8.78% N

Workup

  1. temperatureat reflux for 3 hours
  2. customAt the end of the reaction
  3. temperaturethe reaction was cooled
  4. filtrationfiltered
  5. washthe solids washed with dichloromethane (100 ml)
  6. customthe organic solvent was removed on a rotary evaporator
  7. customto leave a crude oil (18 g)
  8. customPurification
  9. customThe product thus purified
  10. customAnalytically pure sample was prepared

Sources & evidence

ORD record
ord-5ac0164c325848c2b2139193c18ac9ac
Source dataset
uspto-grants-1999_11
Patent number
US05977140

Reaction notes

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