Hydrochloric Acid → 3-[4-({[4'-(2-Ethoxyethoxy)-2',3',5',6'-tetramethylbiphenyl-3-yl]methyl}amino)-2-fluorophenyl]propanoic acid hydrochloride

HRID 508086Notes

Reaction equation

HRID 508086 reaction equation
[CH2:1]([O:3][CH2:4][CH2:5][O:6][C:7]1[C:12]([CH3:13])=[C:11]([CH3:14])[C:10]([C:15]2[CH:20]=[CH:19][CH:18]=[C:17]([CH2:21][NH:22][C:23]3[CH:28]=[CH:27][C:26]([CH2:29][CH2:30][C:31]([O:33]CC)=[O:32])=[C:25]([F:36])[CH:24]=3)[CH:16]=2)=[C:9]([CH3:37])[C:8]=1[CH3:38])[CH3:2].[OH-].[Na+].[ClH:41].Cl.C(OCC)(=O)C>CO.O1CCCC1.C(OCC)(=O)C>[ClH:41].[CH2:1]([O:3][CH2:4][CH2:5][O:6][C:7]1[C:8]([CH3:38])=[C:9]([CH3:37])[C:10]([C:15]2[CH:20]=[CH:19][CH:18]=[C:17]([CH2:21][NH:22][C:23]3[CH:28]=[CH:27][C:26]([CH2:29][CH2:30][C:31]([OH:33])=[O:32])=[C:25]([F:36])[CH:24]=3)[CH:16]=2)=[C:11]([CH3:14])[C:12]=1[CH3:13])[CH3:2]

Participants

8

Reactant 4

HCID 313Hydrochloric AcidHCID 14798Sodium HydroxideHCID 21866389Hydrogen chloride-ethyl acetateHCID 23157425Ethyl 3-[4-({[4'-(2-ethoxyethoxy)-2',3',5',6'-tetramethylbiphenyl-3-yl]methyl}amino)-2-fluorophenyl]propanoate

Product 1

HCID 866243843-[4-({[4'-(2-Ethoxyethoxy)-2',3',5',6'-tetramethylbiphenyl-3-yl]methyl}amino)-2-fluorophenyl]propanoic acid hydrochlorideYield 70%

Reagents, catalysts & solvents 3

HCID 887MethanolSolventHCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent2×

Conditions

Temperature
50 °C

Procedure

To a solution of ethyl 3-[4-({[4′-(2-ethoxyethoxy)-2′,3′,5′,6′-tetramethylbiphenyl-3-yl]methyl}amino)-2-fluorophenyl]propanoate (0.40 g, 0.77 mmol) in a mixture of methanol (4.0 mL) and tetrahydrofuran (8.0 mL) was added 1 N aqueous sodium hydroxide solution (1.53 mL, 1.53 mmol), and the mixture was stirred at 50° C. for 2 hr. The reaction mixture was neutralized with 1 N hydrochloric acid, and diluted with ethyl acetate, and the organic layer was washed with water and saturated brine, dried over anhydrous magnesium sulfate, 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 a colorless oil. The obtained oil was dissolved in ethyl acetate, and 4 N hydrogen chloride/ethyl acetate solution was added. The precipitated crystals were collected by filtration, washed with ethyl acetate, and dried to give the title compound (0.28 g, yield 70%) as colorless crystals.

Workup

  1. washthe organic layer was washed with water and saturated brine
  2. dry with materialdried over anhydrous magnesium sulfate
  3. concentrationconcentrated under reduced pressure
  4. customThe residue was purified by silica gel column chromatography (hexane/ethyl acetate=4/1-hexane/ethyl acetate=1/2)
  5. customto give a colorless oil
  6. filtrationThe precipitated crystals were collected by filtration
  7. washwashed with ethyl acetate
  8. customdried

Sources & evidence

ORD record
ord-ae289b50616a4614a7e800f14306ed35
Source dataset
uspto-grants-2010_08
Patent number
US07786165B2

Reaction notes

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