Potassium Carbonate → 1-(3-Dimethylaminopropyl)-4-(6-fluoro-1,2-benzisoxazol-yl)piperidine difumarate

HRID 975408Notes

Reaction equation

HRID 975408 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.Cl.[CH3:18][N:19]([CH3:24])[CH2:20][CH2:21][CH2:22]Cl.C([O-])([O-])=O.[K+].[K+].[C:31]([OH:38])(=[O:37])/[CH:32]=[CH:33]/[C:34]([OH:36])=[O:35]>S([O-])(O)(=O)=O.C([N+](CCCC)(CCCC)CCCC)CCC.C(#N)C.O.C(O)C>[C:31]([OH:38])(=[O:37])/[CH:32]=[CH:33]/[C:34]([OH:36])=[O:35].[C:31]([OH:38])(=[O:37])/[CH:32]=[CH:33]/[C:34]([OH:36])=[O:35].[CH3:18][N:19]([CH3:24])[CH2:20][CH2:21][CH2:22][N:12]1[CH2:11][CH2:10][CH:9]([C:6]2[C:5]3[CH:15]=[CH:16][C:2]([F:1])=[CH:3][C:4]=3[O:8][N:7]=2)[CH2:14][CH2:13]1

Participants

9

Reactant 4

HCID 11430Potassium CarbonateHCID 943083-(Dimethylamino)propyl chloride hydrochlorideHCID 444972Fumaric AcidHCID 8494213-(4-Piperidyl)-6-fluoro-1,2-benzisoxazole

Product 1

HCID 670711001-(3-Dimethylaminopropyl)-4-(6-fluoro-1,2-benzisoxazol-yl)piperidine difumarateYield 56.9%

Reagents, catalysts & solvents 4

HCID 94433Tetrabutylammonium hydrogen sulfateCatalystHCID 702EthanolSolventHCID 962WaterSolventHCID 6342AcetonitrileSolvent

Conditions

Temperature
60 °C

Procedure

A mixture of 6-fluoro-3-(4-piperidinyl)-1,2-benzisoxazole (3.05 g, 13.8 mmol), 3-dimethylaminopropyl chloride hydrochloride (3.4 g, 21 mmol), K2CO3 (6.2 g, 45 mmol), tetrabutylammonium hydrogen sulfate (phase transfer catalyst, 1.5 g) in acetonitrile (100 ml) and water (50 ml) was heated at 60° C. overnight. The aqueous phase was separated, and acetonitrile was removed at reduced pressure. The residue was extracted into DCM. The organic solution was washed with H2O and brine, then dried with MgSO4. The solvent was removed and the crude product (4.3 g) was treated with fumaric acid (1.58 g, 1.0 eq) in dilute ethanol. The crystals were collected (2.53 g), m.p.=192°-194° C. Recrystallization from ethanol yielded 2.08 g of white crystals, mp=194°-195° C.

Workup

  1. customThe aqueous phase was separated
  2. customacetonitrile was removed at reduced pressure
  3. extractionThe residue was extracted into DCM
  4. washThe organic solution was washed with H2O and brine
  5. dry with materialdried with MgSO4
  6. customThe solvent was removed
  7. customThe crystals were collected (2.53 g), m.p.=192°-194° C
  8. customRecrystallization from ethanol

Sources & evidence

ORD record
ord-d5eb4459d5d24d3fa1f7bf2808c071f3
Source dataset
uspto-grants-1997_03
Patent number
US05607945

Reaction notes

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