N-tert-butyl-2-(3-azido-2-oxo-5-phenyl-2,3,4,5-tetrahydro-1H-(1)benzazepin-1-yl) ethanoic acid amide → N-tert-butyl-2-(3-amino-2-oxo-5-phenyl-2,3,4,5-tetrahydro-1H-(1)benzazepin-1-yl) ethanoic acid amide

HRID 375277

Reaction equation

HRID 375277 reaction equation
[C:1]([NH:5][C:6](=[O:29])[CH2:7][N:8]1[C:14]2[CH:15]=[CH:16][CH:17]=[CH:18][C:13]=2[CH:12]([C:19]2[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=2)[CH2:11][CH:10]([N:25]=[N+]=[N-])[C:9]1=[O:28])([CH3:4])([CH3:3])[CH3:2]>CO.[Pd]>[C:1]([NH:5][C:6](=[O:29])[CH2:7][N:8]1[C:14]2[CH:15]=[CH:16][CH:17]=[CH:18][C:13]=2[CH:12]([C:19]2[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=2)[CH2:11][CH:10]([NH2:25])[C:9]1=[O:28])([CH3:4])([CH3:2])[CH3:3]

Participants

4

Reactant 1

HCID 15203363N-tert-butyl-2-(3-azido-2-oxo-5-phenyl-2,3,4,5-tetrahydro-1H-(1)benzazepin-1-yl) ethanoic acid amide

Product 1

HCID 15203365N-tert-butyl-2-(3-amino-2-oxo-5-phenyl-2,3,4,5-tetrahydro-1H-(1)benzazepin-1-yl) ethanoic acid amideYield 25.9%

Reagents, catalysts & solvents 2

HCID 23938PalladiumCatalystHCID 887MethanolSolvent

Procedure

The crude product from the previous displacement reaction, N-tert-butyl-2-[3-azido-2-oxo-5-phenyl-2,3,4,5-tetrahydro-1H-(1)benzazepin-1-yl] ethanoic acid amide, (8.58 g, 19.37 mmoles), was dissolved in 75 ml methanol under nitrogen. The catalyst, 6 g of 5% Pd/C, 50% w/w, was added and the mixture was hydrogenated at 55 psi H2 for 5 hours. The mixture was filtered through Celite® and the catalyst washed three times with methanol and the filtrate evaporated. TLC (24:1, methylene chloride: methanol, silica gel), showed less polar material and the product at Rf 0.25. The crude product taken up in ethyl acetate and extracted with acid. The acidic extract was back washed with ethyl acetate and then the aqueous fraction was taken with fresh ethyl acetate and the pH adjusted to 10.0. The organic fraction was then dried with brine and sodium sulfate, filtered and concentrated, yielding 1.832 g (25.8%) of the crystalline amine (mp 189°-192° C., one diastereomer). The mother liquor yielded 1.545 g (21.8%) of a foam upon stripping the solvent, which contained nearly a 1:1 mixture of the diastereomers.

Workup

  1. filtrationThe mixture was filtered through Celite®
  2. washthe catalyst washed three times with methanol
  3. customthe filtrate evaporated
  4. extractionextracted with acid
  5. extractionThe acidic extract
  6. washwas back washed with ethyl acetate
  7. dry with materialThe organic fraction was then dried with brine and sodium sulfate
  8. filtrationfiltered
  9. concentrationconcentrated

Sources & evidence

ORD record
ord-3a5b477cffe3406eb3017319acf9422a
Source dataset
uspto-grants-1996_01
Patent number
US05484917

Linked notes

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