Isopropanol → 4-[4-(4-Nitrophenyl)piperazin-1-yl]phenol

HRID 277325Notes

Reaction equation

HRID 277325 reaction equation
[OH:1][C:2]1[CH:7]=[CH:6][C:5]([N:8]2[CH2:13][CH2:12][NH:11][CH2:10][CH2:9]2)=[CH:4][CH:3]=1.Cl[C:15]1[CH:20]=[CH:19][C:18]([N+:21]([O-:23])=[O:22])=[CH:17][CH:16]=1.C(N(CC)C(C)C)(C)C.C(O)(C)C>CN1CCCC1=O>[OH:1][C:2]1[CH:3]=[CH:4][C:5]([N:8]2[CH2:13][CH2:12][N:11]([C:15]3[CH:20]=[CH:19][C:18]([N+:21]([O-:23])=[O:22])=[CH:17][CH:16]=3)[CH2:10][CH2:9]2)=[CH:6][CH:7]=1

Participants

6

Reactant 4

HCID 3776IsopropanolHCID 74741-Chloro-4-nitrobenzeneHCID 81531DiisopropylethylamineHCID 92467p-(1-Piperazinyl)phenol

Product 1

HCID 113810174-[4-(4-Nitrophenyl)piperazin-1-yl]phenol

Reagents, catalysts & solvents 1

HCID 13387N-methyl-2-pyrrolidoneSolvent

Procedure

Under nitrogen, 420 g (2.36 mol) N-(4-Hydroxyphenyl)-piperazine, 520.6 g (3.30 mol) 1-chloro-4-nitrobenzene and 457.5 g (3.54 mol) N,N-Diisopropylethylamine (Hünig's Base) are suspended in 1260 ml N-Methylpyrrolidone and heated to 120°-125° C. The clear solution is stirred at 120°-125° C. and the reaction is followed by HPLC. After complete reaction (5-7 hours) the solution is cooled to 75°-80° C. and 6.3 liters of isopropanol are added over a period of about 30 minutes to the reaction mixture while keeping the temperature at 75°-80° C. (slight heating is necessary). Towards the end of the addition the product starts to precipitate (yellow crystals). The suspension is cooled to 20°-25° C. and stirred overnight at this temperature. Afterwards the suspension is cooled to −10° to −5° C. and stirred for 30 minutes. The product is filtered off, washed with 1.7 liters isopropanol, followed by 5×840 ml warm (35°-40° C.) water. The product is dried under vacuum at 50° C. (slight stream of nitrogen) to constant weight.

Workup

  1. temperatureheated to 120°-125° C
  2. customAfter complete reaction (5-7 hours) the solution
  3. temperatureis cooled to 75°-80° C.
  4. customat 75°-80° C.
  5. temperature(slight heating is necessary)
  6. additionTowards the end of the addition the product
  7. customto precipitate (yellow crystals)
  8. temperatureThe suspension is cooled to 20°-25° C.
  9. stirringstirred overnight at this temperature
  10. temperatureAfterwards the suspension is cooled to −10° to −5° C.
  11. stirringstirred for 30 minutes
  12. filtrationThe product is filtered off
  13. washwashed with 1.7 liters isopropanol
  14. temperaturewarm (35°-40° C.) water
  15. customThe product is dried under vacuum at 50° C. (slight stream of nitrogen) to constant weight

Sources & evidence

ORD record
ord-e560b05bef9f4bb5b7f35a4b1711ca4e
Source dataset
uspto-grants-2002_03
Patent number
US06355801B1

Reaction notes

Loading…