Triethylamine → 2-(3-[4-(4-Fluorophenyl)-1-piperazinyl]-2-hydroxypropyl}naphtho[1,8-cd]isothiazole 1,1-dioxide

HRID 1087518Notes

Reaction equation

HRID 1087518 reaction equation
Br[CH2:2][CH:3]([OH:19])[CH2:4][N:5]1[C:9]2[CH:10]=[CH:11][CH:12]=[C:13]3[CH:14]=[CH:15][CH:16]=[C:7]([C:8]=23)[S:6]1(=[O:18])=[O:17].C(N(CC)CC)C.[F:27][C:28]1[CH:33]=[CH:32][C:31]([N:34]2[CH2:39][CH2:38][NH:37][CH2:36][CH2:35]2)=[CH:30][CH:29]=1>C1(C)C=CC=CC=1>[F:27][C:28]1[CH:29]=[CH:30][C:31]([N:34]2[CH2:39][CH2:38][N:37]([CH2:2][CH:3]([OH:19])[CH2:4][N:5]3[C:9]4[CH:10]=[CH:11][CH:12]=[C:13]5[CH:14]=[CH:15][CH:16]=[C:7]([C:8]=45)[S:6]3(=[O:18])=[O:17])[CH2:36][CH2:35]2)=[CH:32][CH:33]=1

Participants

5

Reactant 3

HCID 8471TriethylamineHCID 752601-(4-Fluorophenyl)piperazineHCID 147267872-(3-Bromo-2-hydroxypropyl)naphtho[1,8-cd]isothiazole 1,1-dioxide

Product 1

HCID 147267882-(3-[4-(4-Fluorophenyl)-1-piperazinyl]-2-hydroxypropyl}naphtho[1,8-cd]isothiazole 1,1-dioxideYield 46.9%

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent

Conditions

Temperature
20 °C

Procedure

2-(3-Bromo-2-hydroxypropyl)naphtho[1,8-cd]isothiazole 1,1-dioxide (26.8 g), triethylamine (11 cc) and 4-(4-fluorophenyl)piperazine (14.1 g) in toluene (280 cc) are heated at boiling point for 8 hours. The mixture is then cooled to a temperature of about 20° C. and stirring is maintained for 15 hours at this temperature. The precipitate formed is separated by filtration and washed with toluene (2×50 cc). The filtrate is evaporated to dryness at 40° C. under reduced pressure (20 mm Hg; 2.7 kPa). The residue obtained is purified by chromatography on a silica column, with ethyl acetate as eluant, and recrystallized from boiling acetonitrile (120 cc). 2-{3-[4-(4-Fluorophenyl)-1-piperazinyl]-2-hydroxypropyl)naphtho[1,8-cd]isothiazole 1,1-dioxide (16.2 g) is obtained, m.p. 130° C.

Workup

  1. customfor 8 hours
  2. temperatureis maintained for 15 hours at this temperature
  3. customThe precipitate formed
  4. customis separated by filtration
  5. washwashed with toluene (2×50 cc)
  6. customThe filtrate is evaporated to dryness at 40° C. under reduced pressure (20 mm Hg; 2.7 kPa)
  7. customThe residue obtained
  8. customis purified by chromatography on a silica column, with ethyl acetate as eluant
  9. customrecrystallized

Sources & evidence

ORD record
ord-12373248edf64ec2839ef69ad2ea407e
Source dataset
uspto-grants-1991_07
Patent number
US05036075

Reaction notes

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