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

HRID 742654Notes

Reaction equation

HRID 742654 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, 18.2 mmol), 1-[4-(4-bromobutoxy)-3-methoxyphenyl]ethanone (6.0 g, 20.0 mmol), K2CO3 (3.0 g, 21.8 mmol), 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.=11.4°-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-c3e15e82edc74badb4bc3c242f317a7d
Source dataset
uspto-grants-1996_09
Patent number
US05554614

Reaction notes

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