Water → Ammonia

HRID 1784900Notes

Reaction equation

HRID 1784900 reaction equation
[Cl:1][C:2]1[CH:20]=[CH:19][C:5]([NH:6][C:7](=[O:18])[C:8]2[CH:13]=[CH:12][CH:11]=[C:10]([OH:14])[C:9]=2[N+:15]([O-])=O)=[CH:4][CH:3]=1.O.[Cl-].[NH4+:23]>CO>[NH3:6].[Cl:1][C:2]1[CH:20]=[CH:19][C:5]([NH:6][C:7](=[O:18])[C:8]2[CH:13]=[CH:12][CH:11]=[C:10]([OH:14])[C:9]=2[NH:15][CH2:7][CH:8]2[CH2:13][CH2:12][N:23]([CH:2]([CH3:20])[CH3:3])[CH2:10][CH2:9]2)=[CH:4][CH:3]=1

Participants

6

Reactant 3

HCID 962WaterHCID 25517Ammonium ChlorideHCID 178569794'-Chloro-3-hydroxy-2-nitrobenzanilide

Product 2

HCID 222AmmoniaHCID 120858924'-Chloro-3-hydroxy-2-{[(1-isopropyl-4-piperidyl)methyl]amino}benzanilide

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Conditions

Temperature
60 °C

Procedure

4′-Chloro-3-hydroxy-2-nitrobenzanilide (1.43 g) was suspended in 50 ml of methanol, then 5 ml of distilled water, 2.80 g of reduced iron and 530 mg of ammonium chloride were added thereto and the mixture was stirred at 60° C. for 2 hours. The reaction was filtered through Celite and concentrated in vacuo. To the resulting residue was added a saturated saline solution and the mixture was extracted with chloroform. The organic layer was dried over magnesium sulfate and concentrated in vacuo. The resulting residue and 320 mg of 1-isopropylpyridine-4-carbaldehyde were suspended in 14 ml of toluene, then 37 mg of p-toluene sulfonic acid hydrate were added thereto and the mixture was heated to reflux for 24 hours together with removal of water by an azeotropic operation. This was concentrated in vacuo, to the resulting residue were added 14 ml of acetic acid and 350 mg of a boran-trimethylamine complex and the mixture was stirred at 70° C. for 17 hours. This was concentrated in vacuo, a 5% aqueous solution of sodium bicarbonate was added to the resulting residue and the mixture was extracted with chloroform. The organic layer was dried over magnesium sulfate and concentrated in vacuo. The resulting residue was purified by means of a silica gel column chromatography using chloroform:methanol:saturated aqueous ammonia (100:10:1) as an eluate to give 380 mg of crudely purified 4′-chloro-3-hydroxy-2-{[(1-isopropyl-4-piperidyl) methyl]amino}benzanilide. The crudely purified product (380 mg) was purified by means of an ODS column chromatography using 0.001N hydrochloric acid:methanol (10:3) as an eluate and then freeze-dried to give 162 mg of 4′-chloro-3-hydroxy-2-{[(1-isopropyl-4-piperidyl) methyl]amino}benzanilide hydrochloride.

Workup

  1. filtrationThe reaction was filtered through Celite
  2. concentrationconcentrated in vacuo
  3. additionTo the resulting residue was added a saturated saline solution
  4. extractionthe mixture was extracted with chloroform
  5. dry with materialThe organic layer was dried over magnesium sulfate
  6. concentrationconcentrated in vacuo
  7. addition37 mg of p-toluene sulfonic acid hydrate were added
  8. temperaturethe mixture was heated
  9. temperatureto reflux for 24 hours together with removal of water by an azeotropic operation
  10. concentrationThis was concentrated in vacuo, to the resulting residue
  11. additionwere added 14 ml of acetic acid and 350 mg of a boran-trimethylamine complex
  12. stirringthe mixture was stirred at 70° C. for 17 hours
  13. concentrationThis was concentrated in vacuo
  14. additiona 5% aqueous solution of sodium bicarbonate was added to the resulting residue
  15. extractionthe mixture was extracted with chloroform
  16. dry with materialThe organic layer was dried over magnesium sulfate
  17. concentrationconcentrated in vacuo
  18. customThe resulting residue was purified by means of a silica gel column chromatography

Sources & evidence

ORD record
ord-29078b7230a741bf84969d79b6bf9c90
Source dataset
uspto-grants-2009_03
Patent number
US07504417B2

Reaction notes

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