Potassium Carbonate → 1-(4-{2-[4-(1,2-Benzothiazol-3-yl)piperazin-1-yl]ethoxy}-3-methoxyphenyl)ethanone

HRID 744478Notes

Reaction equation

HRID 744478 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.Cl[CH2:17][CH2:18][O:19][C:20]1[CH:25]=[CH:24][C:23]([C:26](=[O:28])[CH3:27])=[CH:22][C:21]=1[O:29][CH3:30].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][O:19][C:20]3[CH:25]=[CH:24][C:23]([C:26](=[O:28])[CH3:27])=[CH:22][C:21]=3[O:29][CH3:30])[CH2:3][CH2:2]2)=[N:8]1

Participants

5

Reactant 3

HCID 11430Potassium Carbonate2×HCID 27721443-(1-Piperazinyl)-1,2-benzisothiazoleHCID 144071701-[4-(2-Chloroethoxy)-3-methoxyphenyl]ethanone

Product 1

HCID 164214641-(4-{2-[4-(1,2-Benzothiazol-3-yl)piperazin-1-yl]ethoxy}-3-methoxyphenyl)ethanoneYield 122.8%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Procedure

A mixture of 3-(1-piperazinyl)-1,2-benzisothiazole (4.0 g, 18.2 mmol), 1-[4-(2-chloroethoxy)-3-methoxyphenyl]-ethanone (4.3 g, 20.0 mmol), K2CO3 (3.0 g, 21.8 mmol), acetonitrile (125 ml) and a catalytic amount of KI was heated to reflux and stirred under nitrogen for 24 hours. At this point, an additional amount of K2CO3 (1.0 g, 7.2 mmol) and alkylating agent (0.4 g, 1.7 mmol) was added to the reaction mixture and heating at reflux was resumed for 24 hours. The reaction was cooled to ambient temperature and filtered. The filter cake was washed with acetonitrile and the filtrate was concentrated to afford a dark oil. The oil was extracted with methylene chloride, and the organic extract was washed with water, dried with MgSO4 and concentrated to yield 9.2 g of an oil. Purification by preparative HPLC (Waters Associates Prep LC/System 500 utilizing 2 silica gel columns and 3% methanol/methylene chloride as eluent) provided 3.8 g of a soft, beige gum, which readily solidified. The compound was recrystallized twice from ethanol to give 2.1 g (28%) of -[4-[2-[4-(2-benzisothiazol-3-y)--piperazinyl]ethoxy]-3-methoxyphenyl]ethanone as a beige solid, m.p.=98°-100° C.

Workup

  1. temperaturea catalytic amount of KI was heated
  2. temperatureto reflux
  3. temperatureheating
  4. temperatureat reflux
  5. waitwas resumed for 24 hours
  6. filtrationfiltered
  7. washThe filter cake was washed with acetonitrile
  8. concentrationthe filtrate was concentrated
  9. customto afford a dark oil
  10. extractionThe oil was extracted with methylene chloride
  11. extractionthe organic extract
  12. washwas washed with water
  13. dry with materialdried with MgSO4
  14. concentrationconcentrated

Sources & evidence

ORD record
ord-19c2ababc29044bfa0281e58238011ff
Source dataset
uspto-grants-1996_09
Patent number
US05559126

Reaction notes

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