Citric Acid → HCID 68430400, compound

HRID 384123Notes

Reaction equation

HRID 384123 reaction equation
COC(=O)[CH2:4][C:5]1[CH:10]=[CH:9][C:8]([O:11][CH2:12][C:13]2[CH:18]=[CH:17][CH:16]=[CH:15][C:14]=2[O:19][C:20]2[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=2)=[CH:7][CH:6]=1.C(O)(=O)CC(CC(O)=O)(C(O)=O)O.C[C:41]1([CH3:49])[O:48][C:46](=[O:47])[CH2:45][C:43](=[O:44])O1.Cl.C(N=C=NCCCN(C)C)C>CO.O1CCCC1.[OH-].[Na+].C(Cl)(Cl)Cl.CN(C)C1C=CN=CC=1.O.C1(C)C=CC=CC=1.C(O)C>[O:44]=[C:43]([CH2:4][C:5]1[CH:6]=[CH:7][C:8]([O:11][CH2:12][C:13]2[CH:18]=[CH:17][CH:16]=[CH:15][C:14]=2[O:19][C:20]2[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=2)=[CH:9][CH:10]=1)[CH2:45][C:46]([O:48][CH2:41][CH3:49])=[O:47]

Participants

13

Reactant 4

HCID 311Citric AcidHCID 162492,2-Dimethyl-1,3-dioxane-4,6-dioneHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 131730197Methyl 4-[(2-phenoxyphenyl)methoxy]benzeneacetate

Product 1

HCID 68430400HCID 68430400, compound

Reagents, catalysts & solvents 8

HCID 142844-(Dimethylamino)pyridineCatalystHCID 702EthanolSolventHCID 887MethanolSolventHCID 962WaterSolventHCID 1140TolueneSolventHCID 6212ChloroformSolvent2×HCID 8028TetrahydrofuranSolventHCID 14798Sodium HydroxideSolvent

Procedure

To a mixed solution of methyl(4-((2-phenoxybenzyl)oxy)phenyl)acetate (150 mg) in methanol (2.5 ml) and tetrahydrofuran (1.5 ml), 0.43 ml of 5N aqueous sodium hydroxide was added, and the reaction solution was stirred at room temperature for 1 hour. To the reaction solution was added 10% aqueous citric acid, and the mixture was extracted with chloroform. The combined organic layers were washed with a saturated saline solution and dried over anhydrous magnesium sulfate. The solvent was distilled off under reduced pressure to afford a crude product as a colorless oil. To a solution of the crude product in chloroform (2 ml), 64 mg of Meldrum's acid, 84 mg of 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride, and 110 mg of 4-dimethylaminopyridine were added, and the reaction solution was stirred overnight at room temperature. The reaction solution was diluted with chloroform and water, washed with 5% aqueous citric acid and a saturated saline solution sequentially, and dried over anhydrous magnesium sulfate. The solvent was distilled off under reduced pressure, and the residue obtained was purified by silica gel column chromatography (eluent: chloroform/methanol (98:2)) to afford a colorless oil. To a solution of the resultant oil (100 mg) in toluene (2 ml) was added 0.12 ml of ethanol, and the reaction solution was heated to reflux for 5 hours. The reaction solvent was distilled off under reduced pressure, and the residue obtained was purified by silica gel column chromatography (eluent: hexane/ethyl acetate (90:10-70:30)) to afford the title compound as a colorless oil.

Workup

  1. extractionthe mixture was extracted with chloroform
  2. washThe combined organic layers were washed with a saturated saline solution
  3. dry with materialdried over anhydrous magnesium sulfate
  4. distillationThe solvent was distilled off under reduced pressure
  5. customto afford a crude product as a colorless oil
  6. stirringthe reaction solution was stirred overnight at room temperature
  7. washwashed with 5% aqueous citric acid
  8. dry with materiala saturated saline solution sequentially, and dried over anhydrous magnesium sulfate
  9. distillationThe solvent was distilled off under reduced pressure
  10. customthe residue obtained
  11. customwas purified by silica gel column chromatography (eluent: chloroform/methanol (98:2))
  12. customto afford a colorless oil
  13. temperaturethe reaction solution was heated
  14. temperatureto reflux for 5 hours
  15. distillationThe reaction solvent was distilled off under reduced pressure
  16. customthe residue obtained
  17. customwas purified by silica gel column chromatography (eluent: hexane/ethyl acetate (90:10-70:30))

Sources & evidence

ORD record
ord-da285ff610ef4c8491aa102677ace519
Source dataset
uspto-grants-2013_02
Patent number
US08367708B2

Reaction notes

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