Citric Acid → Benzyl (3S)-3-[(tert-butoxycarbonyl)(methyl)amino]-3-methylpyrrolidine-1-carboxylate

HRID 17634Notes

Reaction equation

HRID 17634 reaction equation
[C:1]([O:5][C:6]([NH:8][C@@:9]1([CH3:24])[CH2:13][CH2:12][N:11]([C:14]([O:16][CH2:17][C:18]2[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=2)=[O:15])[CH2:10]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].CI.[H-].[Na+].[C:29](O)(=O)CC(CC(O)=O)(C(O)=O)O>CN(C)C=O>[C:1]([O:5][C:6]([N:8]([CH3:29])[C@@:9]1([CH3:24])[CH2:13][CH2:12][N:11]([C:14]([O:16][CH2:17][C:18]2[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=2)=[O:15])[CH2:10]1)=[O:7])([CH3:4])([CH3:2])[CH3:3]

Participants

6

Reactant 4

HCID 311Citric AcidHCID 6328Methyl iodideHCID 24758Sodium hydrideHCID 51041670(S)-benzyl 3-(tert-butoxycarbonylamino)-3-methylpyrrolidine-1-carboxylate

Product 1

HCID 51041898Benzyl (3S)-3-[(tert-butoxycarbonyl)(methyl)amino]-3-methylpyrrolidine-1-carboxylateYield 88%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

Benzyl (3S)-3-[(tert-butoxycarbonyl)amino]-3-methylpyrrolidine-1-carboxylate (I-346) (400 mg, 1.20 mmol) and methyl iodide (112 μl, 1.79 mmol) were dissolved in dimethylformamide (12 ml), and with cooling with ice, sodium hydride (55% w/w) (62.6 mg, 1.44 mmol) was added, followed by stirring for 2 hours with cooling with ice. With cooling with ice, aqueous 10% citric acid solution was added to the reaction liquid, followed by extraction with ethyl acetate, and the obtained organic layer was washed with water and saturated brine. After drying over anhydrous sodium sulfate, the insoluble matter was separated by filtration, and the residue obtained by concentration was purified by silica gel column chromatography (eluent, n-hexane:ethyl acetate=2:1, v/v) to obtain the entitled compound (367 mg, 88%) as a colorless oily substance.

Workup

  1. additionwas added
  2. temperaturewith cooling with ice
  3. additionwas added to the reaction liquid
  4. extractionfollowed by extraction with ethyl acetate
  5. washthe obtained organic layer was washed with water and saturated brine
  6. dry with materialAfter drying over anhydrous sodium sulfate
  7. customthe insoluble matter was separated by filtration
  8. customthe residue obtained by concentration
  9. customwas purified by silica gel column chromatography (eluent, n-hexane

Sources & evidence

ORD record
ord-5e6c2b02b5a046d5bbf752bcc3d9985a
Source dataset
uspto-grants-2010_06
Patent number
US07737166B2

Reaction notes

Loading…