Benzyl Chloride → HCID 69686559, compound

HRID 1936631Notes

Reaction equation

HRID 1936631 reaction equation
[C:1]([O:5][C:6]([C@H:8]1[CH2:10][C@@H:9]1[CH:11]1[CH2:15][CH2:14][NH:13][C:12]1=[O:16])=[O:7])([CH3:4])([CH3:3])[CH3:2].[H-].[Na+].[CH2:19](Cl)[C:20]1[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=1.[Cl-].[NH4+]>CN(C)C=O.O1CCCC1>[CH2:19]([N:13]1[CH2:14][CH2:15][CH:11]([C@H:9]2[CH2:10][C@@H:8]2[C:6]([O:5][C:1]([CH3:4])([CH3:2])[CH3:3])=[O:7])[C:12]1=[O:16])[C:20]1[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=1

Participants

7

Reactant 4

HCID 7503Benzyl ChlorideHCID 24758Sodium hydrideHCID 25517Ammonium ChlorideHCID 69686650HCID 69686650, compound

Product 1

HCID 69686559HCID 69686559, compoundYield 46.3%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolvent2×HCID 8028TetrahydrofuranSolvent2×

Procedure

A solution (100 ml) of 8.816 g (39.1 mmol) of 3-[(1R,2S)-2-t-butoxycarbonylcylcopropyl]pyrrolidin-2-one in a 3:2 mixed solvent of tetrahydrofuran and dimethylformamide was added dropwise to 20 ml of a suspension of 1.72 g (43.0 mmol) of sodium hydride in dimethylformamide while cooling with ice, and the mixture was stirred at room temperature for 1.5 hours. Then, 40 ml of a tetrahydrofuran solution of 6.76 ml (58.7 mmol) of benzyl chloride was added dropwise thereto, followed by stirring for 3 hours. After completion of the reaction, a saturated ammonium chloride aqueous solution was added thereto, followed by evaporation under reduced pressure. Water was added to the residue, and the mixture was extracted with ethyl acetate. The organic layer was washed with water and then with a saturated sodium chloride aqueous solution. The organic layer was dried over anhydrous sodium sulfate, and the solvent was evaporated under reduced pressure. The residue was purified by silica gel column chromatography (hexane:ethyl acetate=7:3) to give 5.710 g (44.8%) of 1-benzyl-3-[(1R,2S)-2-t-butoxycarbonylcyclopropyl]pyrrolidin-2-one (isomer A1) as a colorless solid. Then, the column was eluted with a 1:1 mixed solvent of hexane and ethyl acetate to give 3.959 g (31.1%) of 1-benzyl-3-[(1R,2S)-2-t-butoxycarbonylcyclopropyl]pyrrolidin-2-one (isomer B1) as a pale yellow oily substance.

Workup

  1. temperaturewhile cooling with ice
  2. stirringby stirring for 3 hours
  3. customAfter completion of the reaction
  4. customfollowed by evaporation under reduced pressure
  5. additionWater was added to the residue
  6. extractionthe mixture was extracted with ethyl acetate
  7. washThe organic layer was washed with water
  8. dry with materialThe organic layer was dried over anhydrous sodium sulfate
  9. customthe solvent was evaporated under reduced pressure
  10. customThe residue was purified by silica gel column chromatography (hexane:ethyl acetate=7:3)

Sources & evidence

ORD record
ord-b1c7d3cee02a4d8786e1c3a35ae23695
Source dataset
uspto-grants-2002_05
Patent number
US06391889B1

Reaction notes

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