Citric Acid → HCID 66907788, compound

HRID 1691541Notes

Reaction equation

HRID 1691541 reaction equation
[CH2:1]([O:3][CH2:4][CH2:5][O:6][C:7]1[CH:12]=[C:11]([CH3:13])[C:10]([C:14]2[CH:19]=[CH:18][CH:17]=[C:16]([CH2:20][NH:21][C:22]3[CH:27]=[CH:26][C:25]([CH:28]4[CH2:30][CH:29]4[C:31]([O:33]CC)=[O:32])=[C:24]([F:36])[CH:23]=3)[CH:15]=2)=[C:9]([CH3:37])[CH:8]=1)[CH3:2].[OH-].[Na+].C(O)(=O)CC(CC(O)=O)(C(O)=O)O.[ClH:53].C(OCC)(=O)C>C(O)C.O1CCCC1.C(OCC)(=O)C.O>[ClH:53].[CH2:1]([O:3][CH2:4][CH2:5][O:6][C:7]1[CH:8]=[C:9]([CH3:37])[C:10]([C:14]2[CH:19]=[CH:18][CH:17]=[C:16]([CH2:20][NH:21][C:22]3[CH:27]=[CH:26][C:25]([CH:28]4[CH2:30][CH:29]4[C:31]([OH:33])=[O:32])=[C:24]([F:36])[CH:23]=3)[CH:15]=2)=[C:11]([CH3:13])[CH:12]=1)[CH3:2]

Participants

9

Reactant 4

HCID 311Citric AcidHCID 14798Sodium HydroxideHCID 21866389Hydrogen chloride-ethyl acetateHCID 66908116HCID 66908116, compound

Product 1

HCID 66907788HCID 66907788, compoundYield 73%

Reagents, catalysts & solvents 4

HCID 702EthanolSolventHCID 962WaterSolventHCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
50 °C

Procedure

To a mixed solution of ethyl 2-[4-({[4′-(2-ethoxyethoxy)-2′,6′-dimethylbiphenyl-3-yl]methyl}amino)-2-fluorophenyl]cyclopropanecarboxylate (0.451 g, 0.892 mmol) in ethanol (2 mL) and tetrahydrofuran (4 mL) was added 2 M aqueous sodium hydroxide solution (1 mL), and the mixture was stirred at 50° C. for 7 hr. Water was added to the reaction mixture, and the mixture was mildly-acidified with 10% aqueous citric acid solution and extracted with ethyl acetate. The extract was washed with saturated brine, dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (ethyl acetate:hexane=30:70-100:0) to give a yellow oil. To a solution of the obtained oil in ethyl acetate (3.2 mL) was added 4 M hydrogen chloride/ethyl acetate solution (0.8 mL) and the mixture was concentrated under reduced pressure. The residue was crystallized from diethyl ether-ethyl acetate to give the title compound (0.349 g, yield 73%) as colorless crystals.

Workup

  1. extractionextracted with ethyl acetate
  2. washThe extract was washed with saturated brine
  3. dry with materialdried over anhydrous sodium sulfate
  4. concentrationconcentrated under reduced pressure
  5. customThe residue was purified by silica gel column chromatography (ethyl acetate:hexane=30:70-100:0)
  6. customto give a yellow oil
  7. concentrationthe mixture was concentrated under reduced pressure
  8. customThe residue was crystallized from diethyl ether-ethyl acetate

Sources & evidence

ORD record
ord-bd11343aafbe4f5b8439075c63e1acd2
Source dataset
uspto-grants-2012_04
Patent number
US08153694B2

Reaction notes

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