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

HRID 1533364Notes

Reaction equation

HRID 1533364 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, the 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 collect (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 materialthe dried with MgSO4
  6. customThe solvent was removed
  7. customThe crystals were collect (2.53 g), m.p.=192-194° C
  8. customRecrystallization from ethanol

Sources & evidence

ORD record
ord-cb6dfbc460294a8e9c9518e01379b466
Source dataset
uspto-grants-2001_03
Patent number
US06207680B1

Reaction notes

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