Sodium Carbonate → (2R, 4R)-(+)-2-(ethoxycarbonyl)-4-hydroxy-1-(4-methoxy phenethyl) pyrrolidine

HRID 365329Notes

Reaction equation

HRID 365329 reaction equation
Cl.[CH2:2]([O:4][C:5]([C@H:7]1[CH2:11][C@@H:10]([OH:12])[CH2:9][NH:8]1)=[O:6])[CH3:3].C(=O)([O-])[O-].[Na+].[Na+].[CH3:19][O:20][C:21]1[CH:29]=[CH:28][C:24]([CH2:25][CH2:26]Br)=[CH:23][CH:22]=1>C(#N)C.[I-].[Na+]>[CH2:2]([O:4][C:5]([C@H:7]1[CH2:11][C@@H:10]([OH:12])[CH2:9][N:8]1[CH2:26][CH2:25][C:24]1[CH:28]=[CH:29][C:21]([O:20][CH3:19])=[CH:22][CH:23]=1)=[O:6])[CH3:3]

Participants

6

Reactant 3

HCID 10340Sodium CarbonateHCID 844271-(2-Bromoethyl)-4-methoxybenzeneHCID 12709308Ethyl (2R,4R)-4-hydroxypyrrolidine-2-carboxylate hydrochloride

Product 1

HCID 57269395(2R, 4R)-(+)-2-(ethoxycarbonyl)-4-hydroxy-1-(4-methoxy phenethyl) pyrrolidineYield 59.2%

Reagents, catalysts & solvents 2

HCID 5238Sodium IodideCatalystHCID 6342AcetonitrileSolvent

Conditions

Temperature
42.5 °C

Procedure

To a suspension of 6.60 g (33.7 mmol) of (2R,4R)-(+)-2-(ethoxycarbonyl)-4-hydroxypyrrolidine hydrochloride in acetonitrile (60 ml) were added 8.22 g (77.6 mmol) of sodium carbonate, 4-methoxyphenethyl bromide (8.71 g, 40.5 mmol), and sodium iodide (150 mg, 1.0 mmol) and the mixture was stirred at 40-45° C. for 65 h. The mixture was concentrated in vacuo and water was added to the residue, and the products were extracted with ethyl acetate. The extract was washed with saturated aqueous sodium chloride and the products were extracted with 10% aqueous hydrochloride. The extract was washed with ethyl acetate, basified with potassium carbonate and extracted with ethyl acetate. The organic layer was washed with saturated aqueous sodium chloride, dried over anhydrous sodium sulfate, and concentrated in vacuo to obtain oily (2R, 4R)-(+)-2-(ethoxycarbonyl)-4-hydroxy-1-(4-methoxy phenethyl)pyrrolidine (5.85 g, 59.1%).

Workup

  1. concentrationThe mixture was concentrated in vacuo and water
  2. additionwas added to the residue
  3. extractionthe products were extracted with ethyl acetate
  4. washThe extract was washed with saturated aqueous sodium chloride
  5. extractionthe products were extracted with 10% aqueous hydrochloride
  6. washThe extract was washed with ethyl acetate
  7. extractionextracted with ethyl acetate
  8. washThe organic layer was washed with saturated aqueous sodium chloride
  9. dry with materialdried over anhydrous sodium sulfate
  10. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-9ef884667e5e4304bbab77b44a158fac
Source dataset
uspto-grants-2000_10
Patent number
US06127361

Reaction notes

Loading…