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

HRID 2215966Notes

Reaction equation

HRID 2215966 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[Si]([N-][Si](C)(C)C)(C)C.[Li+].[C:21]([O:25][C:26]([N:28]1[CH2:32][CH2:31][CH2:30][CH:29]1[C:33](F)=[O:34])=[O:27])([CH3:24])([CH3:23])[CH3:22]>O1CCCC1.C(OCC)(=O)C>[C:21]([O:25][C:26]([N:28]1[CH2:32][CH2:31][CH2:30][C@@H:29]1[C:33](=[O:34])[NH:1][C:2]1[CH:6]([O:7][CH2:8][CH3:9])[O:5][C:4](=[O:10])[CH:3]=1)=[O:27])([CH3:24])([CH3:23])[CH3:22]

Participants

6

Reactant 3

HCID 2733832Lithium HexamethyldisilazideHCID 14824272Tert-butyl 2-(fluorocarbonyl)pyrrolidine-1-carboxylateHCID 219532364-amino-5-ethoxy-5H-furan-2-one

Product 1

HCID 68576080(R)-2-(2-ethoxy-5-oxo-2,5-dihydrofuran-3-ylcarbamoyl)-pyrrolidine-1-carboxylic acid tert-butyl esterYield 26%

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolvent3×HCID 8857Ethyl AcetateSolvent

Conditions

Temperature
0 °C

Procedure

To a solution of 4-amino-5-ethoxy-5H-furan-2-one (0.08 g, 0.58 mmol) in tetrahydrofuran (10 mL) at −78° C. under nitrogen was dropwise added a solution of 1M lithium bis(trimethylsilyl)amide in tetrahydrofuran (0.64 mL, 0.64 mmol). The reaction was stirred 3 h at 0° C. A solution of 2-fluorocarbonyl-pyrrolidine-1-carboxylic acid tert-butyl ester (0.20 g, 0.77 mmol) in tetrahydrofuran (3 mL) was added dropwise. The reaction was stirred for 16 h at room temperature. The mixture was diluted with ethyl acetate, was washed with 10% sodium bisulfate, saturated sodium bicarbonate, and brine, was dried over sodium sulfate, and was evaporated. Purification by flash chromatography (SiO2) eluted with 35:65 ethyl acetate:hexanes afforded (R )-2-(2-ethoxy-5-oxo-2,5-dihydrofuran-3-ylcarbamoyl)-pyrrolidine-1-carboxylic acid tert-butyl ester (0.05 g, 26% yield). Also isolated was starting 4-amino-5-ethoxy-5H-furan-2-one (0.03 g, 36% yield).

Workup

  1. stirringThe reaction was stirred for 16 h at room temperature
  2. washwas washed with 10% sodium bisulfate, saturated sodium bicarbonate, and brine
  3. dry with materialwas dried over sodium sulfate
  4. customwas evaporated
  5. customPurification by flash chromatography (SiO2)
  6. washeluted with 35:65 ethyl acetate

Sources & evidence

ORD record
ord-54320d7519264a06bfd58d15a624883f
Source dataset
uspto-grants-2006_09
Patent number
US07109357B2

Reaction notes

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