Sodium hydride → 2-{3-[4-(4-Fluorophenyl)-1-piperazinyl]butyl}naphtho[1,8-cd]isothiazole 1,1-dioxide

HRID 1087523Notes

Reaction equation

HRID 1087523 reaction equation
[S:1]1(=[O:14])(=[O:13])[C:5]2=[CH:6][CH:7]=[CH:8][C:9]3=[CH:10][CH:11]=[CH:12][C:3](=[C:4]23)[NH:2]1.[H-].[Na+].Br[CH2:18][CH2:19][CH:20]([N:22]1[CH2:27][CH2:26][N:25]([C:28]2[CH:33]=[CH:32][C:31]([F:34])=[CH:30][CH:29]=2)[CH2:24][CH2:23]1)[CH3:21]>CN(C)C=O>[F:34][C:31]1[CH:30]=[CH:29][C:28]([N:25]2[CH2:24][CH2:23][N:22]([CH:20]([CH3:21])[CH2:19][CH2:18][N:2]3[C:3]4[CH:12]=[CH:11][CH:10]=[C:9]5[CH:8]=[CH:7][CH:6]=[C:5]([C:4]=45)[S:1]3(=[O:13])=[O:14])[CH2:27][CH2:26]2)=[CH:33][CH:32]=1

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 690522H-Naphth(1,8-cd)isothiazole 1,1-dioxideHCID 147267941-(4-Bromo-2-butyl)-4-(4-fluorophenyl)piperazine

Product 1

HCID 147267982-{3-[4-(4-Fluorophenyl)-1-piperazinyl]butyl}naphtho[1,8-cd]isothiazole 1,1-dioxideYield 25.9%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent3×

Conditions

Temperature
20 °C

Procedure

A solution of naphtho[1,8-cd]isothiazole 1,1-dioxide (3.25 g) in dimethylformamide (50 cc) is poured over 30 minutes into a mixture of sodium hydride (0.76 g) in a 50% dispersion in vaseline oil and dimethylformamide (10 cc), under a current of argon. The reaction medium is stirred for 2 hours at a temperature of about 20° C. 1-(4-bromo-2-butyl)-4-(4-fluorophenyl)piperazine (5 g) in dimethylformamide (100 cc) is added over 10 minutes. The reaction mixture is stirred for 15 hours at a temperature close to 20° C., then concentrated to dryness at 40° C. under reduced pressure (20 mm Hg; 2.7 kPa). The residual oil is purified by flash-chromatography on silica column, under a current of argon at medium pressure (0.5-1.5 bar) with a mixture of dichloromethane and ethyl acetate (80-20 vol) as eluant. After recrystallization from boiling acetonitrile (13 cc), 2-{3-[4-(4-fluorophenyl)-1-piperazinyl]butyl}naphtho[1,8-cd]isothiazole 1,1-dioxide (1.8 g) is obtained, m.p. 122° C.

Workup

  1. stirringThe reaction mixture is stirred for 15 hours at a temperature
  2. customclose to 20° C.
  3. concentrationconcentrated to dryness at 40° C. under reduced pressure (20 mm Hg; 2.7 kPa)
  4. customThe residual oil is purified by flash-chromatography on silica column
  5. additionunder a current of argon at medium pressure (0.5-1.5 bar) with a mixture of dichloromethane and ethyl acetate (80-20 vol) as eluant
  6. customAfter recrystallization

Sources & evidence

ORD record
ord-4fb7b1e3f454400caa4ffb2c9bd06e07
Source dataset
uspto-grants-1991_07
Patent number
US05036075

Reaction notes

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