Potassium Carbonate → N-[2-[4-(6-Fluoro-1,2-benzisoxazol-3-yl)-1-piperidinyl]acetyl]-10,11-dihydro-5 H-dibenz[b,f]azepine fumarate

HRID 1739334Notes

Reaction equation

HRID 1739334 reaction equation
ClCC([C:5]1[C:15]2[CH2:14][CH2:13][C:12]3[CH:16]=[CH:17][CH:18]=[CH:19][C:11]=3[NH:10][C:9]=2[CH:8]=[CH:7][CH:6]=1)=O.[F:20][C:21]1[CH:35]=[CH:34][C:24]2[C:25]([CH:28]3[CH2:33][CH2:32][NH:31][CH2:30][CH2:29]3)=[N:26][O:27][C:23]=2[CH:22]=1.C([O-])([O-])=O.[K+].[K+].[C:42]([OH:49])(=[O:48])/[CH:43]=[CH:44]/[C:45]([OH:47])=[O:46]>C(#N)C.C(O)C>[C:42]([OH:49])(=[O:48])/[CH:43]=[CH:44]/[C:45]([OH:47])=[O:46].[F:20][C:21]1[CH:35]=[CH:34][C:24]2[C:25]([CH:28]3[CH2:29][CH2:30][N:31]([CH2:44][C:45]([N:10]4[C:11]5[CH:19]=[CH:18][CH:17]=[CH:16][C:12]=5[CH2:13][CH2:14][C:15]5[CH:5]=[CH:6][CH:7]=[CH:8][C:9]4=5)=[O:46])[CH2:32][CH2:33]3)=[N:26][O:27][C:23]=2[CH:22]=1

Participants

7

Reactant 4

HCID 11430Potassium CarbonateHCID 444972Fumaric AcidHCID 8494213-(4-Piperidyl)-6-fluoro-1,2-benzisoxazoleHCID 15379676HCID 15379676, compound

Product 1

HCID 18467371N-[2-[4-(6-Fluoro-1,2-benzisoxazol-3-yl)-1-piperidinyl]acetyl]-10,11-dihydro-5 H-dibenz[b,f]azepine fumarate

Reagents, catalysts & solvents 2

HCID 702EthanolSolvent2×HCID 6342AcetonitrileSolvent

Procedure

A stirred mixture of 2-chloroacetyl-10,11-dihydro-5H-dibenz[b,f]azepine (6.6 g, 24.3 mmol), 4-(6-fluoro-1,2-benzisoxazol-3-yl)piperidine (5 g, 22.7 mmol) and K2CO3 (3.5 g, 40 mmol) in acetonitrile (300 ml) was heated at reflux for 4 hours. The insolubles were filtered, and the solvent was removed on a rotary evaporator. The crude product was purified by flash chromatography over a silica gel column (100 g of SiO2 ; eluted with dichloromethane (DCM) and 1-2% CH3OH in DCM). The product thus obtained weighed 8.7 g as a yellow oil. A sample (1.5 g) of this material was dissolved in ethanol and was treated with a solution of fumaric acid in ethanol (360 mg/3 ml). The solids collected were recrystallized from acetonitrile to yield 890 mg of white crystals, m.p. 182-183° C.

Workup

  1. temperaturewas heated
  2. temperatureat reflux for 4 hours
  3. filtrationThe insolubles were filtered
  4. customthe solvent was removed on a rotary evaporator
  5. customThe crude product was purified by flash chromatography over a silica gel column (100 g of SiO2 ; eluted with dichloromethane (DCM) and 1-2% CH3OH in DCM)
  6. customThe product thus obtained
  7. customThe solids collected
  8. customwere recrystallized from acetonitrile

Sources & evidence

ORD record
ord-93655d80cc53494792cabb8a385fba2a
Source dataset
uspto-grants-1999_10
Patent number
US05965546

Reaction notes

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