Acetic Acid → HCID 89690562, compound

HRID 1481875Notes

Reaction equation

HRID 1481875 reaction equation
C(O)C.C(O)(=O)C.[Cl:8][C:9]1[CH:28]=[C:27]([N:29]2[CH2:34][CH2:33][N:32]([C:35]3[CH:40]=[C:39]([CH3:41])[CH:38]=[CH:37][C:36]=3[CH3:42])[CH2:31][CH2:30]2)[C:26]([N+:43]([O-])=O)=[CH:25][C:10]=1[C:11]([NH:13][CH2:14][C:15]1[CH:20]=[CH:19][CH:18]=[C:17]([CH2:21][N:22]([CH3:24])[CH3:23])[CH:16]=1)=[O:12]>[Fe]>[NH2:43][C:26]1[C:27]([N:29]2[CH2:30][CH2:31][N:32]([C:35]3[CH:40]=[C:39]([CH3:41])[CH:38]=[CH:37][C:36]=3[CH3:42])[CH2:33][CH2:34]2)=[CH:28][C:9]([Cl:8])=[C:10]([CH:25]=1)[C:11]([NH:13][CH2:14][C:15]1[CH:20]=[CH:19][CH:18]=[C:17]([CH2:21][N:22]([CH3:24])[CH3:23])[CH:16]=1)=[O:12]

Participants

5

Reactant 3

HCID 176Acetic AcidHCID 702EthanolHCID 89690493HCID 89690493, compound

Product 1

HCID 89690562HCID 89690562, compoundYield 70%

Reagents, catalysts & solvents 1

HCID 23925IronCatalyst

Conditions

Temperature
75 °C

Procedure

In a 250 ml round bottom flask equipped with a magnetic stir bar and a septum with a nitrogen inlet, the iron powder (557.40 mg, 9.98 mmol) was suspended in clean, dry, reagent-grade ethanol (50.00 ml, 856.34 mmol) and the mixture was stirred together vigorously under nitrogen at room temperature as the acetic acid (5.00 ml, 87.34 mmol) was added. The reaction continued to stir at room temperature as the 2-chloro-N-(3-dimethylaminomethyl-benzyl)-4-[4-(2,5-dimethyl-phenyl)-piperazin-1-yl]-5-nitro-benzamide 13a (214.40 mg, 0.40 mmol) was added in one portion. The reaction mixture was then warmed to 75° C. and the reaction stirred for 4 h. After 4 h, the reaction was cooled to room temperature and filtered through Celite, washing with methanol. The solvent was then removed from the filtrate under reduced pressure. The ruby red oil was then taken back up in 100 ml of ethyl acetate; an equivalent amount of saturated aqueous NaHCO3 solution was added to the organic solution. The layers were then separated and the aqueous layer was extracted with ethyl acetate (2×75 ml). The organic phases were combined and dried over Na2SO4. The product solution was then decanted and the solvent was removed under reduced pressure. The crude product, 5-amino-2-chloro-N-(3-dimethylaminomethyl-benzyl)-4-[4-(2,5-dimethyl-phenyl)-piperazin-1-yl]-benzamide 13b (142.50 mg, 0.28 mmol), was isolated as a brown solid and was carried on without further purification. LCMS (m/e)=507 (M+H).

Workup

  1. customIn a 250 ml round bottom flask equipped with a magnetic stir bar
  2. customin clean, dry
  3. additionwas added
  4. additionwas added in one portion
  5. waitAfter 4 h
  6. temperaturethe reaction was cooled to room temperature
  7. filtrationfiltered through Celite
  8. washwashing with methanol
  9. customThe solvent was then removed from the filtrate under reduced pressure
  10. additionan equivalent amount of saturated aqueous NaHCO3 solution was added to the organic solution
  11. customThe layers were then separated
  12. extractionthe aqueous layer was extracted with ethyl acetate (2×75 ml)
  13. dry with materialdried over Na2SO4
  14. customThe product solution was then decanted
  15. customthe solvent was removed under reduced pressure

Sources & evidence

ORD record
ord-3e1c76d9ba594a059ee4c493388f6d41
Source dataset
uspto-grants-2016_08
Patent number
US09409897B2

Reaction notes

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