Citric Acid → HCID 86751034, compound

HRID 263684Notes

Reaction equation

HRID 263684 reaction equation
C([N-]C(C)C)(C)C.[Li+].[CH2:9]([O:11][C:12](=[O:21])[C@H:13]([CH2:15][C:16]([O:18][CH2:19][CH3:20])=[O:17])[OH:14])[CH3:10].Br[CH2:23][C:24]([O:26][CH2:27][C:28]1[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=1)=[O:25].C(O)(=O)[CH2:35][C:36](CC(O)=O)(C(O)=O)[OH:37]>O1CCCC1.C1CCCCC1>[C:36]([O:14][C@H:13]([C:12]([O:11][CH2:9][CH3:10])=[O:21])[C@H:15]([C:16]([O:18][CH2:19][CH3:20])=[O:17])[CH2:23][C:24]([O:26][CH2:27][C:28]1[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=1)=[O:25])(=[O:37])[CH3:35]

Participants

7

Reactant 4

HCID 311Citric AcidHCID 62576Benzyl bromoacetateHCID 1715085Diethyl L-malateHCID 2724682Lithium diisopropylamide

Product 1

HCID 86751034HCID 86751034, compound

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolvent3×HCID 8078CyclohexaneSolvent

Conditions

Temperature
-20 °C

Procedure

5.2 ml of a 2M cyclohexane solution of lithium diisopropylamide was dissolved in 10 ml of tetrahydrofuran, and 5 ml of a tetrahydrofuran solution containing 2 g of (S)-malic acid diethyl ester, was dropwise added at -78° C. under a nitrogen atmosphere. The reaction solution was gradually heated to -20° C. over a period of one hour and then again cooled to -78° C. Then, 5 ml of a tetrahydrofuran solution containing 1.32 g of benzyl bromoacetate was added thereto, followed by stirring for one hour at -78° C. to -20° C. 10 ml of a 1N citric acid aqueous solution was added thereto and extracted with ethyl ether. Then, the ether layer was washed with a saturated sodium chloride aqueous solution and dried over anhydrous sodium sulfate. The drying agent was filtered off, and then, the solvent was distilled off under reduced pressure. The residue was purified by silica gel column chromatography (hexane/ethyl acetate=10/1→3/1). The obtained (1S,2R)-1-hydroxy-1,2,3-propanetricarboxylic acid 3-benzyl 1,2-diethyl ester was dissolved in 6 ml of pyridine, and 3 ml of acetic anhydride was added thereto, followed by stirring at room temperature for 12 hours. The reaction solution was evaporated to dryness under reduced pressure, and then residue was purified by silica gel column chromatography (hexane/ethyl acetate=3/1) to obtain 966 mg of the above-identified compound as colorless oily substance.

Workup

  1. additionwas dropwise added at -78° C. under a nitrogen atmosphere
  2. temperatureagain cooled to -78° C
  3. additionwas added
  4. extractionextracted with ethyl ether
  5. washThen, the ether layer was washed with a saturated sodium chloride aqueous solution
  6. dry with materialdried over anhydrous sodium sulfate
  7. filtrationThe drying agent was filtered off
  8. distillationthe solvent was distilled off under reduced pressure
  9. customThe residue was purified by silica gel column chromatography (hexane/ethyl acetate=10/1→3/1)
  10. dissolutionThe obtained (1S,2R)-1-hydroxy-1,2,3-propanetricarboxylic acid 3-benzyl 1,2-diethyl ester was dissolved in 6 ml of pyridine
  11. addition3 ml of acetic anhydride was added
  12. stirringby stirring at room temperature for 12 hours
  13. customThe reaction solution was evaporated to dryness under reduced pressure
  14. customresidue was purified by silica gel column chromatography (hexane/ethyl acetate=3/1)

Sources & evidence

ORD record
ord-03a57f1a91754179b6520024023d879e
Source dataset
uspto-grants-1997_07
Patent number
US05643958

Reaction notes

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