Hydrochloric Acid → 3-[4-({2',6'-Dimethyl-4'-[(6-methylpyridin-2-yl)methoxy]biphenyl-3-yl}methoxy)-2-fluorophenyl]propanoic acid hydrochloride

HRID 273418Notes

Reaction equation

HRID 273418 reaction equation
[CH3:1][C:2]1[CH:7]=[C:6]([O:8][CH2:9][C:10]2[CH:15]=[CH:14][CH:13]=[C:12]([CH3:16])[N:11]=2)[CH:5]=[C:4]([CH3:17])[C:3]=1[C:18]1[CH:23]=[CH:22][CH:21]=[C:20]([CH2:24][O:25][C:26]2[CH:31]=[CH:30][C:29]([CH2:32][CH2:33][C:34]([O:36]CC)=[O:35])=[C:28]([F:39])[CH:27]=2)[CH:19]=1.[OH-].[Na+].[ClH:42].C(OCC)(=O)C.Cl>C(OCC)(=O)C.O1CCCC1.CO>[ClH:42].[CH3:1][C:2]1[CH:7]=[C:6]([O:8][CH2:9][C:10]2[CH:15]=[CH:14][CH:13]=[C:12]([CH3:16])[N:11]=2)[CH:5]=[C:4]([CH3:17])[C:3]=1[C:18]1[CH:23]=[CH:22][CH:21]=[C:20]([CH2:24][O:25][C:26]2[CH:31]=[CH:30][C:29]([CH2:32][CH2:33][C:34]([OH:36])=[O:35])=[C:28]([F:39])[CH:27]=2)[CH:19]=1

Participants

8

Reactant 4

HCID 313Hydrochloric AcidHCID 14798Sodium HydroxideHCID 21866389Hydrogen chloride-ethyl acetateHCID 58903176Ethyl 3-[4-({2',6'-dimethyl-4'-[(6-methylpyridin-2-yl)methoxy]biphenyl-3-yl}methoxy)-2-fluorophenyl]propanoate

Product 1

HCID 693115433-[4-({2',6'-Dimethyl-4'-[(6-methylpyridin-2-yl)methoxy]biphenyl-3-yl}methoxy)-2-fluorophenyl]propanoic acid hydrochlorideYield 86%

Reagents, catalysts & solvents 3

HCID 887MethanolSolventHCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent2×

Procedure

To a mixture of ethyl 3-[4-({2′,6′-dimethyl-4′-[(6-methylpyridin-2-yl)methoxy]biphenyl-3-yl}methoxy)-2-fluorophenyl]propanoate (1.30 g, 2.46 mmol), methanol (6 mL) and tetrahydrofuran (10 mL) was added 1 N sodium hydroxide aqueous solution (4.9 mL) at room temperature with stirring, and the mixture was stirred at the same temperature for 2 hrs. The reaction mixture was neutralized 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-ethyl acetate) to give an oil. The oil was dissolved in ethyl acetate and 4 N hydrogen chloride-ethyl acetate solution was added. The precipitated crystals were collected by filtration, washed and dried to give the title compound (1.14 g, yield 86%) as colorless crystals.

Workup

  1. stirringthe mixture was stirred at the same temperature for 2 hrs
  2. washwashed with saturated brine
  3. customdried
  4. concentrationconcentrated under reduced pressure
  5. customThe residue was purified by silica gel column chromatography (hexane/ethyl acetate=4/1-ethyl acetate)
  6. customto give an oil
  7. filtrationThe precipitated crystals were collected by filtration
  8. washwashed
  9. customdried

Sources & evidence

ORD record
ord-cb9c8762a9314e25b3fd894057fe6a4e
Source dataset
uspto-grants-2008_11
Patent number
US07456218B2

Reaction notes

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