Potassium Carbonate → 2-[4-(6-Fluoro-1,2-benzisoxazol-3-yl)-1-piperidinyl]ethyl acetate fumarate

HRID 1420388Notes

Reaction equation

HRID 1420388 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]([O:26][CH2:27][CH2:28]Br)(=[O:25])[CH3:24].[C:30]([OH:37])(=[O:36])/[CH:31]=[CH:32]/[C:33]([OH:35])=[O:34]>C(#N)C.C(O)C>[C:30]([OH:37])(=[O:36])/[CH:31]=[CH:32]/[C:33]([OH:35])=[O:34].[C:23]([O:26][CH2:27][CH2:28][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)(=[O:25])[CH3:24]

Participants

7

Reactant 4

HCID 11430Potassium CarbonateHCID 135641-Acetoxy-2-bromoethaneHCID 444972Fumaric AcidHCID 8494213-(4-Piperidyl)-6-fluoro-1,2-benzisoxazole

Product 1

HCID 219600152-[4-(6-Fluoro-1,2-benzisoxazol-3-yl)-1-piperidinyl]ethyl acetate fumarate

Reagents, catalysts & solvents 2

HCID 702EthanolSolvent2×HCID 6342AcetonitrileSolvent

Procedure

A mixture of 6-fluoro-3-(4-piperidinyl)-1,2-benzisoxazole (3.0 g, 13.6 mmol), K2CO3 (3.5 g, 25 mmol), 2-bromoethyl acetate (4 g, 26.5 mmol) in acetonitrile (50 ml) was heated at reflux for 4 hours. After cooling to room temperature, the inorganic salts were filtered and washed with DCM (dichloromethane 50 ml). The organic solvent was removed on a rotary evaporator to give an oil. The oily product was purified on a flash chromatography column (60 g of SiO2 ; eluted with MeOH 2%-4% in DCM). The pure product thus obtained weighed 4.43 g. This oil was dissolved in ethanol and treated with a solution of fumaric acid (1.2 g) in ethanol. The salt crystallized out at room temperature to yield 3.44 g (57%), m.p.=154°-155° C.

Workup

  1. temperaturewas heated
  2. temperatureat reflux for 4 hours
  3. filtrationthe inorganic salts were filtered
  4. washwashed with DCM (dichloromethane 50 ml)
  5. customThe organic solvent was removed on a rotary evaporator
  6. customto give an oil
  7. customThe oily product was purified on a flash chromatography column (60 g of SiO2 ; eluted with MeOH 2%-4% in DCM)
  8. customThe pure product thus obtained
  9. customThe salt crystallized out at room temperature
  10. customto yield 3.44 g (57%), m.p.=154°-155° C.

Sources & evidence

ORD record
ord-274eb315c2de4367ac7403ce495122a8
Source dataset
uspto-grants-1999_03
Patent number
US05889035

Reaction notes

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