Ammonium Chloride → Tert-butyl 4-allyl-3-[(2-aminophenyl)carbamoyl]-3-[(trifluoroacetyl)amino]pyrrolidine-1-carboxylate

HRID 61389Notes

Reaction equation

HRID 61389 reaction equation
[CH2:1]([CH:4]1[CH2:8][N:7]([C:9]([O:11][C:12]([CH3:15])([CH3:14])[CH3:13])=[O:10])[CH2:6][C:5]1([C:23](=[O:34])[NH:24][C:25]1[CH:30]=[CH:29][CH:28]=[CH:27][C:26]=1[N+:31]([O-])=O)[NH:16][C:17](=[O:22])[C:18]([F:21])([F:20])[F:19])[CH:2]=[CH2:3].[Cl-].[NH4+]>CO.C(OCC)(=O)C.[Zn]>[CH2:1]([CH:4]1[CH2:8][N:7]([C:9]([O:11][C:12]([CH3:15])([CH3:14])[CH3:13])=[O:10])[CH2:6][C:5]1([C:23](=[O:34])[NH:24][C:25]1[CH:30]=[CH:29][CH:28]=[CH:27][C:26]=1[NH2:31])[NH:16][C:17](=[O:22])[C:18]([F:20])([F:21])[F:19])[CH:2]=[CH2:3]

Participants

6

Reactant 2

HCID 25517Ammonium ChlorideHCID 86665787Tert-butyl 4-allyl-3-[(2-nitrophenyl)carbamoyl]-3-[(trifluoroacetyl)amino]pyrrolidine-1-carboxylate

Product 1

HCID 86665788Tert-butyl 4-allyl-3-[(2-aminophenyl)carbamoyl]-3-[(trifluoroacetyl)amino]pyrrolidine-1-carboxylateYield 99.1%

Reagents, catalysts & solvents 3

HCID 23994ZincCatalystHCID 887MethanolSolventHCID 8857Ethyl AcetateSolvent

Procedure

A solution of tert-butyl 4-allyl-3-[(2-nitrophenyl)carbamoyl]-3-[(trifluoroacetyl)amino]pyrrolidine-1-carboxylate (0.816 g, 1.68 mmol) in methanol (30 mL) was treated with ammonium chloride (0.897 g, 16.8 mmol) and zinc (2.19 g, 33.5 mmol). After stirring at room temperature for 40 min, the mixture was diluted with ethyl acetate (30 mL) and filtered through a pad of Celite. The pad was washed with ethyl acetate and the filtrate was concentrated under reduced pressure. The residue was re-diluted with ethyl acetate (25 mL) and water (20 mL), and the layers were separated. The organic phase was washed with water (10 mL) and saturated aqueous sodium chloride (10 mL), dried over Na2SO4 and concentrated and dried under high vacuum for ˜2 h to give the tert-butyl 4-allyl-3-[(2-aminophenyl)carbamoyl]-3-[(trifluoroacetyl)amino]pyrrolidine-1-carboxylate intermediate (760 mg, 3:2 mixture of diastereomers) as a off-white foam that was used without further purification.

Workup

  1. filtrationfiltered through a pad of Celite
  2. washThe pad was washed with ethyl acetate
  3. concentrationthe filtrate was concentrated under reduced pressure
  4. additionThe residue was re-diluted with ethyl acetate (25 mL) and water (20 mL)
  5. customthe layers were separated
  6. washThe organic phase was washed with water (10 mL) and saturated aqueous sodium chloride (10 mL)
  7. dry with materialdried over Na2SO4
  8. concentrationconcentrated
  9. customdried under high vacuum for ˜2 h

Sources & evidence

ORD record
ord-298fbd0c3adb4c1ba391ad542a1243ce
Source dataset
uspto-grants-2016_09
Patent number
US09440995B2

Reaction notes

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