Potassium Carbonate → 1-[4-[4-[4-(1,2-Benzisothiazol-3-yl)-1-piperazinyl]butoxy]3-methoxyphenyl]ethanone

HRID 2257611Notes

Reaction equation

HRID 2257611 reaction equation
[N:1]1([C:7]2[C:11]3[CH:12]=[CH:13][CH:14]=[CH:15][C:10]=3[S:9][N:8]=2)[CH2:6][CH2:5][NH:4][CH2:3][CH2:2]1.Br[CH2:17][CH2:18][CH2:19][CH2:20][O:21][C:22]1[CH:27]=[CH:26][C:25]([C:28](=[O:30])[CH3:29])=[CH:24][C:23]=1[O:31][CH3:32].C([O-])([O-])=O.[K+].[K+]>C(#N)C>[S:9]1[C:10]2[CH:15]=[CH:14][CH:13]=[CH:12][C:11]=2[C:7]([N:1]2[CH2:6][CH2:5][N:4]([CH2:17][CH2:18][CH2:19][CH2:20][O:21][C:22]3[CH:27]=[CH:26][C:25]([C:28](=[O:30])[CH3:29])=[CH:24][C:23]=3[O:31][CH3:32])[CH2:3][CH2:2]2)=[N:8]1

Participants

5

Reactant 3

HCID 11430Potassium CarbonateHCID 27721443-(1-Piperazinyl)-1,2-benzisothiazoleHCID 144071711-[4-(4-Bromobutoxy)3-methoxyphenyl]ethanone

Product 1

HCID 158400161-[4-[4-[4-(1,2-Benzisothiazol-3-yl)-1-piperazinyl]butoxy]3-methoxyphenyl]ethanoneYield 39%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Procedure

A mixture of 3-(1-piperazinyl)-1,2-benzisothiazole (4.0 g, 0.0182 mol), 1-[4-(4-bromobutoxy)-3-methoxyphenyl]ethanone (6.0 g, 0.0200 mol), K2CO3 (3.0 g, 0.0218 mol), KI (200 mg), and acetonitrile (125 ml) was stirred at reflux under N2 for 5 hours. Most of the solvent was removed in vacuo and the resultant gummy residue was partitioned between ethyl acetate and water. The organic extract was washed with water, dried with MgSO4, and concentrated to yield 7.8 g. Purification by preparative HPLC (Waters Associates Prep LC/System 500, utilizing 2 silica gel columns and 4% methanol-methylene chloride as eluent) afforded 6.5 g of a damp, off-white solid. The product was recrystallized twice from toluene to provide 3.1 g (39%) of 1-[4-[4-[4-(1,2-benzisothiazol-3-yl)-1-piperazinyl]butoxy]-3-methoxyphenyl]ethanone as a white solid, m.p.=114°-116° C.

Workup

  1. temperatureat reflux under N2 for 5 hours
  2. customMost of the solvent was removed in vacuo
  3. customthe resultant gummy residue was partitioned between ethyl acetate and water
  4. extractionThe organic extract
  5. washwas washed with water
  6. dry with materialdried with MgSO4
  7. concentrationconcentrated
  8. customto yield 7.8 g
  9. customPurification by preparative HPLC (Waters Associates Prep LC/System 500, utilizing 2 silica gel columns and 4% methanol-methylene chloride as eluent)
  10. customafforded 6.5 g of a damp, off-white solid
  11. customThe product was recrystallized twice from toluene

Sources & evidence

ORD record
ord-18922bf6b0c34f509a421ffd666fd394
Source dataset
uspto-grants-1997_08
Patent number
US05658911

Reaction notes

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