1,2-Dichloroethane → (R)-2-(2-ethoxy-5-oxo-tetrahydrofuran-3-ylcarbamoyl)-pyrrolidine-1-carboxylic acid tert-butyl ester

HRID 2215956Notes

Reaction equation

HRID 2215956 reaction equation
[N:1]([CH:4]1[CH:8]([O:9][CH2:10][CH3:11])[O:7][C:6](=[O:12])[CH2:5]1)=[N+]=[N-].[C:13]([O:17][C:18]([N:20]1[CH2:24][CH2:23][CH2:22][C@H:21]1[C:25](O)=[O:26])=[O:19])([CH3:16])([CH3:15])[CH3:14].C(N(C(C)C)CC)(C)C.C(Cl)CCl.C1C=CC2N(O)N=NC=2C=1>[Pd].C(OCC)(=O)C>[C:13]([O:17][C:18]([N:20]1[CH2:24][CH2:23][CH2:22][C@@H:21]1[C:25](=[O:26])[NH:1][CH:4]1[CH2:5][C:6](=[O:12])[O:7][CH:8]1[O:9][CH2:10][CH3:11])=[O:19])([CH3:16])([CH3:15])[CH3:14]

Participants

8

Reactant 5

HCID 111,2-DichloroethaneHCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 850831,2-Pyrrolidinedicarboxylic acid, 1-(1,1-dimethylethyl) ester, (2S)-HCID 112982094-Azido-5-ethoxy-dihydrofuran-2-one

Product 1

HCID 68578131(R)-2-(2-ethoxy-5-oxo-tetrahydrofuran-3-ylcarbamoyl)-pyrrolidine-1-carboxylic acid tert-butyl esterYield 56.1%

Reagents, catalysts & solvents 2

HCID 23938PalladiumCatalystHCID 8857Ethyl AcetateSolvent2×

Procedure

A mixture of 4-azido-5-ethoxy-dihydrofuran-2-one (1.06 g, 6.2 mmol), (S)-pyrrolidine-1,2-dicarboxylic acid 1-tert-butyl ester (1.33 g, 6.2 mmol), and 10% palladium on carbon (0.50 g) in ethyl acetate previously degassed with N2 (50 mL) was stirred under 1 atm hydrogen at room temperature for 1 h. The mixture was diluted with dichloromethane, filtered (Celite) and evaporated. The crude mixture was dissolved in dichloromethane (100 mL), was treated with diisopropylethylamine (5.4 mL, 30.8 mmol), EDC (1.48 g, 7.71 mmol), and HOBT (1.04 g, 7.71 mmol) and was stirred at room temperature under nitrogen for 24 h. The reaction 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 1:1 ethyl acetate:hexanes provided (R)-2-(2-ethoxy-5-oxo-tetrahydrofuran-3-ylcarbamoyl)-pyrrolidine-1-carboxylic acid tert-butyl ester (1.19 g, 56% yield) as a very viscous, pale yellow oil. 1H-NMR (500 MHz, CDCl3) δ 7.61 (br, 0.6H), 5.29 (s, 0.6H), 5.25 (br s, 0.4H), 4.29 (br, 1.2H), 4.20 (br s, 0.8H), 3.78 (m, 1H), 3.57 (m, 1H), 3.34 (br, 1.4H), 3.25 (br, 0.6H), 2.94 (br dd, J=14.9, 3.8 Hz, 1H), 2.31 (dd, J=18.0, 1.4 Hz, 1H), 2.1-2.3 (br 1H), 1.82 (br s, 1H), 1.39 (s, 9H), 1.17 (m, 3H) ppm. MS (ES+): m/e=343 (M+H).

Workup

  1. custompreviously degassed with N2 (50 mL)
  2. additionThe mixture was diluted with dichloromethane
  3. filtrationfiltered (Celite)
  4. customevaporated
  5. dissolutionThe crude mixture was dissolved in dichloromethane (100 mL)
  6. stirringwas stirred at room temperature under nitrogen for 24 h
  7. washwas washed with 10% sodium bisulfate, saturated sodium bicarbonate, and brine
  8. dry with materialwas dried over sodium sulfate
  9. customwas evaporated
  10. customPurification by flash chromatography (SiO2)
  11. washeluted with 1:1 ethyl acetate

Sources & evidence

ORD record
ord-6f1f07441ccd45b49f49f4735904f773
Source dataset
uspto-grants-2006_09
Patent number
US07109357B2

Reaction notes

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