Citric Acid → Diethyl (1-benzhydryl-3-azetidinyl)malonate

HRID 1457995Notes

Reaction equation

HRID 1457995 reaction equation
[C:1]([O:9][CH2:10][CH3:11])(=[O:8])[CH2:2][C:3]([O:5][CH2:6][CH3:7])=[O:4].[H-].[Na+].[CH:14]([N:27]1[CH2:30][CH:29](OS(C2C=CC(C)=CC=2)(=O)=O)[CH2:28]1)([C:21]1[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=1)[C:15]1[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=1.C(O)(=O)CC(CC(O)=O)(C(O)=O)O>O1CCCC1>[CH:14]([N:27]1[CH2:30][CH:29]([CH:2]([C:3]([O:5][CH2:6][CH3:7])=[O:4])[C:1]([O:9][CH2:10][CH3:11])=[O:8])[CH2:28]1)([C:21]1[CH:22]=[CH:23][CH:24]=[CH:25][CH:26]=1)[C:15]1[CH:16]=[CH:17][CH:18]=[CH:19][CH:20]=1

Participants

6

Reactant 4

HCID 311Citric AcidHCID 7761Diethyl MalonateHCID 24758Sodium hydrideHCID 155126511-Benzhydrylazetidin-3-yl 4-methylbenzenesulfonate

Product 1

HCID 11132697Diethyl (1-benzhydryl-3-azetidinyl)malonate

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

To 17.90 g (111.80 mmol) of diethyl malonate dissolved in 250 ml of tetrahydrofuran was added 4.07 g (101.75 mmol) of 60% sodium hydride at room temperature, followed by 2 hours of stirring. Thereafter, thereto was added 20 g (50.82 mmol) of 1-benzhydryl-3-(p-toluenesulfonyloxy)azetidine which has been dissolved in 90 ml of tetrahydrofuran, followed by 1 week of heating under reflux. The reaction solution was mixed with 10% citric acid aqueous solution and then tetrahydrofuran was evaporated. The resulting residue was mixed with saturated sodium bicarbonate aqueous solution, extracted with chloroform (200 ml×3) and dried over anhydrous sodium sulfate. After evaporation of the solvent, the resulting residue was purified by a silica gel column chromatography (230-400 mesh silica gel 450 ml, ethyl acetate:hexane 1:3) to yield quantitative amount of the title compound.

Workup

  1. waitfollowed by 1 week
  2. temperatureof heating
  3. temperatureunder reflux
  4. customtetrahydrofuran was evaporated
  5. additionThe resulting residue was mixed with saturated sodium bicarbonate aqueous solution
  6. extractionextracted with chloroform (200 ml×3)
  7. dry with materialdried over anhydrous sodium sulfate
  8. customAfter evaporation of the solvent
  9. customthe resulting residue was purified by a silica gel column chromatography (230-400 mesh silica gel 450 ml, ethyl acetate:hexane 1:3)

Sources & evidence

ORD record
ord-cd384e23442b42ad984c40d17755528c
Source dataset
uspto-grants-1998_12
Patent number
US05849757

Reaction notes

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