Tert-butyl 2-(fluorocarbonyl)pyrrolidine-1-carboxylate → (R)-2-(2-ethoxy-5-oxo-2,5-dihydrofuran-3-ylcarbamoyl)-pyrrolidine-1-carboxylic acid tert-butyl ester

HRID 2215967Notes

Reaction equation

HRID 2215967 reaction equation
[NH2:1][C:2]1[CH:6]([O:7][CH2:8][CH3:9])[O:5][C:4](=[O:10])[CH:3]=1.[C:11]([O:15][C:16]([N:18]1[CH2:22][CH2:21][CH2:20][CH:19]1[C:23](F)=[O:24])=[O:17])([CH3:14])([CH3:13])[CH3:12].CC(C)([O-])C.[Na+]>O1CCCC1.C(OCC)(=O)C>[C:11]([O:15][C:16]([N:18]1[CH2:22][CH2:21][CH2:20][C@@H:19]1[C:23](=[O:24])[NH:1][C:2]1[CH:6]([O:7][CH2:8][CH3:9])[O:5][C:4](=[O:10])[CH:3]=1)=[O:17])([CH3:14])([CH3:13])[CH3:12]

Participants

6

Reactant 3

HCID 14824272Tert-butyl 2-(fluorocarbonyl)pyrrolidine-1-carboxylateHCID 219532364-amino-5-ethoxy-5H-furan-2-oneHCID 23676156Sodium t-butoxide

Product 1

HCID 68576080(R)-2-(2-ethoxy-5-oxo-2,5-dihydrofuran-3-ylcarbamoyl)-pyrrolidine-1-carboxylic acid tert-butyl esterYield 63%

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a solution of 4-amino-5-ethoxy-5H-furan-2-one (0.05 g, 0.35 mmol) and 2-fluorocarbonyl-pyrrolidine-1-carboxylic acid tert-butyl ester (0.09 g, 0.42 mmol) in tetrahydrofuran (5 mL) at room temperature under nitrogen was added sodium tert-butoxide(0.05 g, 0.49 mmol). The reaction was stirred 3 h at reflux. After cooling, the mixture was diluted with ethyl acetate, was washed with 10% potassium bisulfate, saturated sodium bicarbonate, and brine, was dried over sodium sulfate, and was evaporated. Purification by flash chromatography (SiO2) eluted with 4:6 ethyl acetate:hexanes afforded (R)-2-(2-ethoxy-5-oxo-2,5-dihydrofuran-3-ylcarbamoyl)-pyrrolidine-1-carboxylic acid tert-butyl ester (0.075 g, 63% yield). Also recovered was starting 4-amino-5-ethoxy-5H-furan-2-one (0.016 g, 32% yield).

Workup

  1. temperatureat reflux
  2. temperatureAfter cooling
  3. washwas washed with 10% potassium bisulfate, saturated sodium bicarbonate, and brine
  4. dry with materialwas dried over sodium sulfate
  5. customwas evaporated
  6. customPurification by flash chromatography (SiO2)
  7. washeluted with 4:6 ethyl acetate

Sources & evidence

ORD record
ord-cce37314d8c443d0956bbf9fc7c4bfb1
Source dataset
uspto-grants-2006_09
Patent number
US07109357B2

Reaction notes

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