Hydrochloric Acid → HCID 58903147, compound

HRID 273407Notes

Reaction equation

HRID 273407 reaction equation
[OH:1][C:2]1[CH:7]=[C:6]([CH3:8])[C:5]([C:9]2[CH:14]=[CH:13][CH:12]=[C:11]([CH2:15][O:16][C:17]3[CH:22]=[CH:21][C:20]([CH2:23][CH2:24][C:25]([O:27]C)=[O:26])=[CH:19][CH:18]=3)[CH:10]=2)=[C:4]([CH3:29])[CH:3]=1.C(=O)([O-])[O-].[K+].[K+].[I-].[Na+].[CH3:38][O:39][CH2:40]Cl.[OH-].[Na+].Cl>CN(C)C=O.C(OCC)(=O)C.O1CCCC1.CO>[CH3:38][O:39][CH2:40][O:1][C:2]1[CH:7]=[C:6]([CH3:8])[C:5]([C:9]2[CH:14]=[CH:13][CH:12]=[C:11]([CH2:15][O:16][C:17]3[CH:18]=[CH:19][C:20]([CH2:23][CH2:24][C:25]([OH:27])=[O:26])=[CH:21][CH:22]=3)[CH:10]=2)=[C:4]([CH3:29])[CH:3]=1

Participants

11

Reactant 6

HCID 313Hydrochloric AcidHCID 5238Sodium IodideHCID 7864Chloromethyl Methyl EtherHCID 11430Potassium CarbonateHCID 14798Sodium HydroxideHCID 57413460HCID 57413460, compound

Product 1

HCID 58903147HCID 58903147, compoundYield 22.3%

Reagents, catalysts & solvents 4

HCID 887MethanolSolventHCID 6228DimethylformamideSolventHCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent2×

Procedure

To a solution of methyl 3-{4-[(4′-hydroxy-2′,6′-dimethylbiphenyl-3-yl)methoxy]phenyl}propanoate (0.50 g, 1.28 mmol), potassium carbonate (0.35 g, 2.56 mmol) and sodium iodide (0.19 g, 1.28 mmol) in N,N-dimethylformamide (5.0 mL) was added chloromethyl methyl ether (0.13 mL, 1.66 mmol) at room temperature with stirring and the mixture was stirred at 50° C. for 24 hrs. The reaction mixture was diluted with ethyl acetate, washed with water and saturated brine, dried and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (hexane/ethyl acetate=10/1-hexane/ethyl acetate=3/1) to give a colorless oil. Then, to a mixture of the oil, methanol (4 mL) and tetrahydrofuran (8 mL) was added 1 N aqueous sodium hydroxide solution (2.6 mL) at room temperature with stirring, and the mixture was stirred at the same temperature for 2 hrs. The reaction mixture was adjusted to pH3 with 1 N hydrochloric acid, diluted with ethyl acetate, washed with saturated brine, dried and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (hexane/ethyl acetate=4/1-hexane/ethyl acetate=1/2) to give the title compound (0.12 g, yield 22%) as colorless crystals.

Workup

  1. stirringthe mixture was stirred at 50° C. for 24 hrs
  2. washwashed with water and saturated brine
  3. customdried
  4. concentrationconcentrated under reduced pressure
  5. customThe residue was purified by silica gel column chromatography (hexane/ethyl acetate=10/1-hexane/ethyl acetate=3/1)
  6. customto give a colorless oil
  7. stirringwith stirring
  8. stirringthe mixture was stirred at the same temperature for 2 hrs
  9. washwashed with saturated brine
  10. customdried
  11. concentrationconcentrated under reduced pressure
  12. customThe residue was purified by silica gel column chromatography (hexane/ethyl acetate=4/1-hexane/ethyl acetate=1/2)

Sources & evidence

ORD record
ord-1eb8ef7c0c1547019b8a53533a96d6a3
Source dataset
uspto-grants-2008_11
Patent number
US07456218B2

Reaction notes

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