2,2,2-Trifluoroethylamine hydrochloride → 1-benzyl-5-oxo-N-(2,2,2-trifluoroethyl)pyrrolidine-3-carboxamide

HRID 2372048Notes

Reaction equation

HRID 2372048 reaction equation
[O:1]=[C:2]1[N:6]([CH2:7][C:8]2[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=2)[CH2:5][CH:4]([C:14]([O:16]C)=O)[CH2:3]1.C(C1NC=CN=1)(C1NC=CN=1)=O.Cl.[F:31][C:32]([F:36])([F:35])[CH2:33][NH2:34].N12CCCN=C1CCCCC2>O1CCCC1>[O:1]=[C:2]1[N:6]([CH2:7][C:8]2[CH:9]=[CH:10][CH:11]=[CH:12][CH:13]=2)[CH2:5][CH:4]([C:14]([NH:34][CH2:33][C:32]([F:36])([F:35])[F:31])=[O:16])[CH2:3]1

Participants

6

Reactant 4

HCID 97722,2,2-Trifluoroethylamine hydrochlorideHCID 811841,8-Diazabicyclo(5.4.0)undec-7-eneHCID 98909Methyl 1-benzyl-5-oxopyrrolidine-3-carboxylateHCID 5250894Bis-(1H-imidazol-2-YL)-methanone

Product 1

HCID 134917961-benzyl-5-oxo-N-(2,2,2-trifluoroethyl)pyrrolidine-3-carboxamideYield 28.3%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
0 °C

Procedure

A mixture of 21.9 g (0.10 mole) methyl 5-oxo-1-(phenylmethyl)-3-pyrrolidinecarboxylate in 150 ml tetrahydrofuran, was cooled to 0° C. in an ice bath under nitrogen and 24.3 g (0.15 mole) carbonyl diimidazole was added. The reaction was stirred at 0° C. for 30 minutes, then at room temperature for 30 minutes. A solution of 13.6 g (0.10 mole) of 2,2,2-trifluoroethylamine hydrochloride, 15.2 g (0.10 mole) 1,8-diazabicyclo[5.4.0]undec-7-ene and 100 ml tetrahydrofuran was added. The reaction was stirred at room temperature overnight. The solvent was removed at reduced pressure. The residue was taken up in dichloromethane and washed 3×150 ml saturated sodium bicarbonate. The organic layer was dried over magnesium sulfate and the solvent removed under reduced pressure. The product was purified by column chromatography on silica with ethyl acetate to give 8.50 g of 5-oxo-1-(phenylmethyl)-N-(2,2,2-trifluoroethyl)-3-pyrrolidinecarboxamide, mp 110-112° C.

Workup

  1. waitat room temperature for 30 minutes
  2. stirringThe reaction was stirred at room temperature overnight
  3. customThe solvent was removed at reduced pressure
  4. washwashed 3×150 ml saturated sodium bicarbonate
  5. dry with materialThe organic layer was dried over magnesium sulfate
  6. customthe solvent removed under reduced pressure
  7. customThe product was purified by column chromatography on silica with ethyl acetate

Sources & evidence

ORD record
ord-e964f3fe5b06493babafbc13d62bcda1
Source dataset
uspto-grants-1992_03
Patent number
US05097032

Reaction notes

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