2,2,2-Trifluoroethanol → Tert-butyl 4-allyl-3-[(2-nitrophenyl)carbamoyl]-3-[(trifluoroacetyl)amino]pyrrolidine-1-carboxylate

HRID 61388Notes

Reaction equation

HRID 61388 reaction equation
[CH2:1]([CH:4]1[C:8](=O)[CH2:7][N:6]([C:10]([O:12][C:13]([CH3:16])([CH3:15])[CH3:14])=[O:11])[CH2:5]1)[CH:2]=[CH2:3].[F:17][C:18]([F:23])([F:22])[C:19]([O-])=[O:20].[NH4+:24].[N+:25]([C:28]1[CH:33]=[CH:32][CH:31]=[CH:30][C:29]=1[N+:34]#[C-])([O-:27])=[O:26].FC(F)(F)[CH2:38][OH:39]>C(OCC)(=O)C>[CH2:1]([CH:4]1[CH2:5][N:6]([C:10]([O:12][C:13]([CH3:16])([CH3:15])[CH3:14])=[O:11])[CH2:7][C:8]1([C:38](=[O:39])[NH:34][C:29]1[CH:30]=[CH:31][CH:32]=[CH:33][C:28]=1[N+:25]([O-:27])=[O:26])[NH:24][C:19](=[O:20])[C:18]([F:23])([F:22])[F:17])[CH:2]=[CH2:3]

Participants

6

Reactant 4

HCID 64092,2,2-TrifluoroethanolHCID 2724268Ammonium trifluoroacetateHCID 154458841-Isocyano-2-nitrobenzeneHCID 67513550Tert-butyl 3-allyl-4-oxopyrrolidine-1-carboxylate

Product 1

HCID 86665787Tert-butyl 4-allyl-3-[(2-nitrophenyl)carbamoyl]-3-[(trifluoroacetyl)amino]pyrrolidine-1-carboxylateYield 51%

Reagents, catalysts & solvents 1

HCID 8857Ethyl AcetateSolvent

Procedure

While under nitrogen, a stirred mixture of tert-butyl 3-allyl-4-oxopyrrolidine-1-carboxylate (600 mg, 2.66 mmol), ammonium trifluoroacetate (698 mg, 5.33 mmol) and 2-nitrophenyl isocyanide (690 mg, 4.6 mmol) in 2,2,2-trifluoroethanol (2.7 mL) was placed in a 60° C. oil bath and stirred overnight. After cooling to room temperature, the mixture was diluted with ethyl acetate (40 mL), washed with water (3×20 mL) and the combined aqueous phase was re-extracted with ethyl acetate (20 mL). The combined organic phase was washed with saturated aqueous sodium chloride (20 mL), dried over Na2SO4 and concentrated under reduced pressure. Purification by silica gel chromatography (90 g column, 0-5% ethyl acetate in methylene chloride) gave tert-butyl 4-allyl-3-[(2-nitrophenyl)carbamoyl]-3-[(trifluoroacetyl)amino]-pyrrolidine-1-carboxylate (665 mg, 51%, 3:2 mixture of diastereomers) as an amber gum. LC-MS ESI+ MS found for C21H25F3N4O6 m/z 509.0 (M+Na). LC-MS ESI−MS found for C21H25F3N4O6 m/z 485.1 (M−H).

Workup

  1. customwas placed in a 60° C.
  2. washwashed with water (3×20 mL)
  3. extractionthe combined aqueous phase was re-extracted with ethyl acetate (20 mL)
  4. washThe combined organic phase was washed with saturated aqueous sodium chloride (20 mL)
  5. dry with materialdried over Na2SO4
  6. concentrationconcentrated under reduced pressure
  7. customPurification by silica gel chromatography (90 g column, 0-5% ethyl acetate in methylene chloride)

Sources & evidence

ORD record
ord-48a73c5cc1cc48ff86a60b4f3d0d8d74
Source dataset
uspto-grants-2016_09
Patent number
US09440995B2

Reaction notes

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