Pyridine → Tert-butoxycarbonyl-4-(ethoxyimino)-2-pyrrolidinecarboxylic acid

HRID 457909Notes

Reaction equation

HRID 457909 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:12][C:11](=O)[CH2:10][C@H:9]1[C:14]([OH:16])=[O:15])=[O:7])([CH3:4])([CH3:3])[CH3:2].Cl.[CH2:18]([O:20][NH2:21])[CH3:19].N1C=CC=CC=1>C(O)C>[C:1]([O:5][C:6]([N:8]1[CH2:12][C:11](=[N:21][O:20][CH2:18][CH3:19])[CH2:10][CH:9]1[C:14]([OH:16])=[O:15])=[O:7])([CH3:4])([CH3:3])[CH3:2]

Participants

5

Reactant 3

HCID 1049PyridineHCID 76850O-ethylhydroxylamine hydrochlorideHCID 11593804(2S)-1-(tert-butoxycarbonyl)-4-oxopyrrolidine-2-carboxylic acid

Product 1

HCID 73854946Tert-butoxycarbonyl-4-(ethoxyimino)-2-pyrrolidinecarboxylic acidYield 93%

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Procedure

A solution was made containing (2S)-1-(tert-butoxycarbonyl)-4-oxo-2-pyrrolidinecarboxylic acid (5.0 g, 22 mmol) and O-ethylhydroxylamine hydrochloride (6.4 g, 65.5 mmol) in a 1:1 mixture of pyridine and ethanol (100 ml). The reaction was heated to reflux for 2.5 h before cooling and removal of solvent. The residue was dissolved in ethyl acetate and washed rapidly with 1.3N HCl (40 ml). The acidic layer was then extracted with ethyl acetate (3×20 ml) and the combined organic layers washed with brine before drying over magnesiom sulfate, filtering and removal of solvent in vacuo. The desired product (5.5 g, 93%) was isolated as a pale yellow oil.

Workup

  1. temperatureThe reaction was heated
  2. temperatureto reflux for 2.5 h
  3. temperaturebefore cooling
  4. customremoval of solvent
  5. dissolutionThe residue was dissolved in ethyl acetate
  6. washwashed rapidly with 1.3N HCl (40 ml)
  7. extractionThe acidic layer was then extracted with ethyl acetate (3×20 ml)
  8. washthe combined organic layers washed with brine
  9. dry with materialbefore drying over magnesiom sulfate
  10. filtrationfiltering
  11. customremoval of solvent in vacuo

Sources & evidence

ORD record
ord-e7966bd5b30842398c6704890a8d2452
Source dataset
uspto-grants-2007_03
Patent number
US07189754B2

Reaction notes

Loading…