Hydrochloric Acid → FK-960

HRID 277324Notes

Reaction equation

HRID 277324 reaction equation
[OH-].[Na+].C(N1CCN(C(N)=O)CC1)(=O)C.Cl[O-].[Na+].[C:18]([N:21]1[CH2:26][CH2:25][N:24]([NH:27][C:28](=[O:30])O)[CH2:23][CH2:22]1)(=[O:20])[CH3:19].Cl.[F:32][C:33]1[CH:41]=[CH:40][C:36](C(Cl)=O)=[CH:35][CH:34]=1>O1CCCC1.O>[C:18]([N:21]1[CH2:22][CH2:23][N:24]([NH:27][C:28](=[O:30])[C:36]2[CH:40]=[CH:41][C:33]([F:32])=[CH:34][CH:35]=2)[CH2:25][CH2:26]1)(=[O:20])[CH3:19]

Participants

9

Reactant 6

HCID 313Hydrochloric AcidHCID 14798Sodium Hydroxide2×HCID 678794-Fluorobenzoyl chlorideHCID 48302761-Piperazinecarboxamide, 4-acetyl-HCID 183145424-Acetyl-1-piperazinylcarbamic acidHCID 23665760Sodium Hypochlorite

Product 1

HCID 181428FK-960

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent2×

Procedure

1 N Aqueous sodium hydroxide (70 ml) and water (30 ml) were cooled at 5 to 10° C., and 4-acetyl-1-piperazinecarboxamide (10.0 g) was added thereto and dissolved under stirring. 10% Aqueous sodium hypochlorite (43.5 ml) was added in one portion thereto at the same temperature and allowed to react for 1 hour at the same temperature, and after the temperature was raised, the mixture was further reacted for 2 hours at a temperature of 15 to 20° C. The reaction solution containing 4-acetyl-1-piperazinylcarbamic acid was adjusted to pH 6.5-7.5 with 1 N hydrochloric acid (about 23 ml), followed by adding tetrahydrofuran (100 ml). A solution of 4-fluorobenzoyl chloride (11.1 g) in tetrahydrofuran (20 ml) was added dropwise thereto at 20 to 30° C. over the period of 1 hour. Because the pH was decreased during the addition, the reaction solution was kept at pH 6.0 to 7.0 with 1 N aqueous sodium hydroxide. After this dropwise addition was finished, the solution was further reacted for 2 hours at the same temperature and at the same pH. The reaction solution was concentrated to 50 ml under reduced pressure, then cooled on ice and stirred at 5 to 10° C. for 1 hour to precipitate N-(4-acetyl-1-piperazinyl)-4-fluorobenzamide. The resultant crystals were collected at the same temperature by filtration, washed with cold water (50 ml) and dried under reduced pressure to give N-(4-acetyl-1-piperazinyl)-4-fluorobenzamide (8.35 g). NMR (DMSO-d6, δ): 2.03 (3H, s), 2.77-2.92 (4H, m), 3.50-3.52 (4H, m), 7.23-7.34 (2H, m), 7.82-7.89 (2H, m), 9.58 (1H, s)

Workup

  1. dissolutiondissolved
  2. customto react for 1 hour at the same temperature
  3. temperatureafter the temperature was raised
  4. customthe mixture was further reacted for 2 hours at a temperature of 15 to 20° C
  5. customat 20 to 30° C.
  6. customover the period of 1 hour
  7. additionBecause the pH was decreased during the addition
  8. additionAfter this dropwise addition
  9. customthe solution was further reacted for 2 hours at the same temperature and at the same pH
  10. concentrationThe reaction solution was concentrated to 50 ml under reduced pressure
  11. temperaturecooled on ice
  12. stirringstirred at 5 to 10° C. for 1 hour
  13. customto precipitate N-(4-acetyl-1-piperazinyl)-4-fluorobenzamide
  14. filtrationThe resultant crystals were collected at the same temperature by filtration
  15. washwashed with cold water (50 ml)
  16. customdried under reduced pressure

Sources & evidence

ORD record
ord-afb24cad09c24a2e921daec7b05af185
Source dataset
uspto-grants-2002_03
Patent number
US06355800B1

Reaction notes

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