Hydrochloric Acid → 3-(2-fluoro-4-[(4-{[3-(4-fluorophenyl)-5-(2-phenylethyl)-1H-pyrazol-1-yl]methyl}benzyl)oxy]phenyl}propanoic acid

HRID 2110915Notes

Reaction equation

HRID 2110915 reaction equation
[F:1][C:2]1[CH:7]=[C:6]([O:8][CH2:9][C:10]2[CH:15]=[CH:14][C:13]([CH2:16][N:17]3[C:21]([CH2:22][CH2:23][C:24]4[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=4)=[CH:20][C:19]([C:30]4[CH:35]=[CH:34][C:33]([F:36])=[CH:32][CH:31]=4)=[N:18]3)=[CH:12][CH:11]=2)[CH:5]=[CH:4][C:3]=1[CH2:37][CH2:38][C:39]([O:41]CC)=[O:40].[OH-].[Na+].Cl>CO.O1CCCC1>[F:1][C:2]1[CH:7]=[C:6]([O:8][CH2:9][C:10]2[CH:15]=[CH:14][C:13]([CH2:16][N:17]3[C:21]([CH2:22][CH2:23][C:24]4[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=4)=[CH:20][C:19]([C:30]4[CH:31]=[CH:32][C:33]([F:36])=[CH:34][CH:35]=4)=[N:18]3)=[CH:12][CH:11]=2)[CH:5]=[CH:4][C:3]=1[CH2:37][CH2:38][C:39]([OH:41])=[O:40]

Participants

6

Reactant 3

HCID 313Hydrochloric AcidHCID 14798Sodium HydroxideHCID 23159974ethyl 3-{2-fluoro-4-[(4-{[3-(4-fluorophenyl)-5-(2-phenylethyl)-1H-pyrazol-1-yl]methyl}benzyl)oxy]phenyl}propanoate

Product 1

HCID 231599533-(2-fluoro-4-[(4-{[3-(4-fluorophenyl)-5-(2-phenylethyl)-1H-pyrazol-1-yl]methyl}benzyl)oxy]phenyl}propanoic acidYield 11%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 8028TetrahydrofuranSolvent

Procedure

The oil obtained in Example 142 was dissolved in methanol (5 mL) and tetrahydrofuran (5 mL), and 2 N aqueous sodium hydroxide solution (2 mL) was added. The mixture was stirred at room temperature for 1 hr. The reaction mixture was neutralized with 6 N hydrochloric acid, and the mixture was extracted with ethyl acetate. The ethyl acetate layer was dried using a Presep Dehydration tube (Manufactured by Wako Pure Chemical Industries, Ltd.), and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (hexane:ethyl acetate=9:1-1:4) to give the title compound (61 mg, yield 11%, 2 steps) as colorless crystals. 1H NMR (CDCl3) δ: 2.62 (2H, t, J=7.5 Hz), 2.79-2.93 (6H, m), 4.98 (2H, s), 5.24 (2H, s), 6.37 (1H, s), 6.59-6.68 (2H, m), 7.03-7.14 (7H, m), 7.18-7.38 (5H, m), 7.76 (2H, dd, J=8.9, 5.5 Hz).

Workup

  1. extractionthe mixture was extracted with ethyl acetate
  2. dry with materialThe ethyl acetate layer was dried
  3. concentrationconcentrated under reduced pressure
  4. customThe residue was purified by silica gel column chromatography (hexane:ethyl acetate=9:1-1:4)

Sources & evidence

ORD record
ord-9d88e7e8d1ff44adbb93614c906675a1
Source dataset
uspto-grants-2009_04
Patent number
US07517910B2

Reaction notes

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