Citric Acid → HCID 68585159, compound

HRID 17636Notes

Reaction equation

HRID 17636 reaction equation
[CH3:1][C@:2]1([NH:16][C:17](=[O:23])[O:18][C:19]([CH3:22])([CH3:21])[CH3:20])[CH2:6][C:5](=[O:7])[N:4]([C@@H:8]([C:10]2[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=2)[CH3:9])[CH2:3]1.CI.[H-].[Na+].[C:28](O)(=O)CC(CC(O)=O)(C(O)=O)O>CN(C)C=O>[CH3:28][N:16]([C@@:2]1([CH3:1])[CH2:6][C:5](=[O:7])[N:4]([C@@H:8]([C:10]2[CH:11]=[CH:12][CH:13]=[CH:14][CH:15]=2)[CH3:9])[CH2:3]1)[C:17](=[O:23])[O:18][C:19]([CH3:22])([CH3:21])[CH3:20]

Participants

6

Reactant 4

HCID 311Citric AcidHCID 6328Methyl iodideHCID 24758Sodium hydrideHCID 51041667tert-Butyl {(3S)-3-methyl-5-oxo-1-[(1R)-1-phenylethyl]pyrrolidin-3-yl}carbamate

Product 1

HCID 68585159HCID 68585159, compoundYield 96%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

Tert-Butyl {(3S)-3-methyl-5-oxo-1-[(1R)-1-phenylethyl]pyrrolidin-3-yl}carbamate (I-343) (4.08 g, 12.8 mmol) and methyl iodide (1.20 ml, 19.2 mmol) were dissolved in N,N-dimethylformamide (120 ml), and with cooling with ice, sodium hydride (55% w/w) (671 mg, 15.4 mmol) was added, followed by stirring for 1 hour with cooling with ice. With cooling with ice, aqueous 10% citric acid solution was added to the reaction liquid, followed by concentration under reduced pressure. The resulting residue was dissolved in ethyl acetate, washed with saturated brine, and dried over anhydrous sodium sulfate, then the insoluble was separated by filtration, and the residue obtained by concentration was purified by silica gel column chromatography (eluent, n-hexane:ethyl acetate=2:1→1:4, v/v) to obtain tert-butyl methyl-{(3S)-3-methyl-5-oxo-1-[(1R)-1-phenylethyl]pyrrolidin-3-yl}carbamate (4.09 g, 96%) as a colorless oily substance.

Workup

  1. additionwas added
  2. temperaturewith cooling with ice
  3. additionwas added to the reaction liquid
  4. concentrationfollowed by concentration under reduced pressure
  5. dissolutionThe resulting residue was dissolved in ethyl acetate
  6. washwashed with saturated brine
  7. dry with materialdried over anhydrous sodium sulfate
  8. customthe insoluble was separated by filtration
  9. customthe residue obtained by concentration
  10. customwas purified by silica gel column chromatography (eluent, n-hexane:ethyl acetate=2:1→1:4, v/v)

Sources & evidence

ORD record
ord-363bcda4cc3048f2a8012fd3d7d2e29d
Source dataset
uspto-grants-2010_06
Patent number
US07737166B2

Reaction notes

Loading…