Citric Acid → Ethyl 3-[1-benzyloxy-3-(isoamyloxycarbonyl)cyclobutan-3-yl]-3-oxopropionate

HRID 1279658Notes

Reaction equation

HRID 1279658 reaction equation
[CH2:1]([O:8][CH:9]1[CH2:12][C:11]([C:16]([O:18][CH2:19][CH2:20][CH:21]([CH3:23])[CH3:22])=[O:17])([C:13](O)=[O:14])[CH2:10]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.C1N=CN(C(N2C=N[CH:33]=[CH:32]2)=O)C=1.C([CH:38](C([O-])=O)[C:39]([O-:41])=[O:40])C.[Mg+2].C(O)(=O)CC(CC(O)=O)(C(O)=O)O>O1CCCC1.C(OCC)(=O)C>[CH2:1]([O:8][CH:9]1[CH2:10][C:11]([C:13](=[O:14])[CH2:38][C:39]([O:41][CH2:32][CH3:33])=[O:40])([C:16]([O:18][CH2:19][CH2:20][CH:21]([CH3:23])[CH3:22])=[O:17])[CH2:12]1)[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1

Participants

7

Reactant 4

HCID 311Citric AcidHCID 682631,1'-CarbonyldiimidazoleHCID 184277961-Benzyloxy-3-(isoamyloxycarbonyl)cyclobutane-3-carboxylic acidHCID 22261989Magnesium ethylmalonate

Product 1

HCID 18427818Ethyl 3-[1-benzyloxy-3-(isoamyloxycarbonyl)cyclobutan-3-yl]-3-oxopropionate

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolvent2×HCID 8857Ethyl AcetateSolvent

Procedure

A 21.49 g (67.08 mmol) portion of 1-benzyloxy-3-(isoamyloxycarbonyl)cyclobutane-3-carboxylic acid was dissolved in 200 ml of tetrahydrofuran to which, while cooling in an ice bath with stirring, was added 13.05 g (80.49 mmol) of N,N-carbonyldiimidazole. After 10 minutes of 2stirring, the ice bath was detached and the reaction mixture was stirred at room temperature for 3 hours. To the reaction solution which was cooled in an ice bath and stirred was added dropwise 100 ml of tetrahydrofuran solution containing 23.06 g (80.49 mmol) of magnesium ethylmalonate. After 1 hour of stirring, the ice bath was detached, and the reaction mixture was stirred at room temperature for 10 hours. While cooling in an ice bath and stirring, the reaction mixture was mixed with 10% citric acid aqueous solution and then with ethyl acetate to effect separation of layers, and the resulting organic layer was washed with saturated sodium bicarbonate aqueous solution and saturated brine. The organic layer was dried over anhydrous sodium sulfate and filtered, the solvent was evaporated under a reduced pressure and then the resulting residue was purified by a silica gel column chromatography (n-hexane:ethyl acetate=2:1) to give 11.37 g (29.12 mmol) of the title compound.

Workup

  1. temperaturewhile cooling in an ice bath
  2. stirringthe reaction mixture was stirred at room temperature for 3 hours
  3. temperatureTo the reaction solution which was cooled in an ice bath
  4. stirringstirred
  5. stirringAfter 1 hour of stirring
  6. stirringthe reaction mixture was stirred at room temperature for 10 hours
  7. temperatureWhile cooling in an ice bath
  8. stirringstirring
  9. customseparation of layers
  10. washthe resulting organic layer was washed with saturated sodium bicarbonate aqueous solution and saturated brine
  11. dry with materialThe organic layer was dried over anhydrous sodium sulfate
  12. filtrationfiltered
  13. customthe solvent was evaporated under a reduced pressure
  14. customthe resulting residue was purified by a silica gel column chromatography (n-hexane:ethyl acetate=2:1)

Sources & evidence

ORD record
ord-0c12fd3a852b4e3b90915edd7c8da128
Source dataset
uspto-grants-2002_09
Patent number
US06448266B1

Reaction notes

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