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

HRID 2110892Notes

Reaction equation

HRID 2110892 reaction equation
[C:1]1([CH2:7][CH2:8][C:9]2[NH:13][N:12]=[C:11]([C:14]3[CH:19]=[CH:18][C:17]([C:20]([F:23])([F:22])[F:21])=[CH:16][CH:15]=3)[CH:10]=2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[H-].[Na+].Cl[CH2:27][C:28]1[CH:47]=[CH:46][C:31]([CH2:32][O:33][C:34]2[CH:39]=[CH:38][C:37]([CH2:40][CH2:41][C:42]([O:44]C)=[O:43])=[CH:36][CH:35]=2)=[CH:30][CH:29]=1.Cl>CO.O1CCCC1.[OH-].[Na+].O.CN(C)C=O>[C:1]1([CH2:7][CH2:8][C:9]2[N:13]([CH2:27][C:28]3[CH:47]=[CH:46][C:31]([CH2:32][O:33][C:34]4[CH:39]=[CH:38][C:37]([CH2:40][CH2:41][C:42]([OH:44])=[O:43])=[CH:36][CH:35]=4)=[CH:30][CH:29]=3)[N:12]=[C:11]([C:14]3[CH:15]=[CH:16][C:17]([C:20]([F:23])([F:22])[F:21])=[CH:18][CH:19]=3)[CH:10]=2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1

Participants

10

Reactant 4

HCID 313Hydrochloric Acid2×HCID 24758Sodium hydrideHCID 23082857Methyl 3-(4-([4-(chloromethyl)benzyl]oxy)phenyl)propanoateHCID 231573735-(2-phenylethyl)-3-[4-(trifluoromethyl)phenyl]-1H-pyrazole

Product 1

HCID 115560953-(4-{[4-({5-(2-phenylethyl)-3-[4-(trifluoromethyl)phenyl]-1H-pyrazol-1-yl}methyl)benzyl]oxy}phenyl)propanoic acidYield 94.1%

Reagents, catalysts & solvents 5

HCID 887MethanolSolventHCID 962WaterSolventHCID 6228DimethylformamideSolventHCID 8028TetrahydrofuranSolventHCID 14798Sodium HydroxideSolvent

Procedure

A mixture of 5-(2-phenylethyl)-3-[4-(trifluoromethyl)phenyl]-1H-pyrazole (350 mg, 1.11 mmol), sodium hydride (60% in oil, 40 mg, 1.00 mmol) and N,N-dimethylformamide (5 mL) was stirred at room temperature for 1 hr. Methyl 3-(4-([4-(chloromethyl)benzyl]oxy)phenyl)propanoate (318 mg, 1.00 mmol) was added to the reaction mixture at room temperature and the mixture was further stirred at room temperature for 1 hr. The reaction mixture was poured into 1N 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=19:1-1:1) to give a yellow oil. The yellow oil was dissolved in a mixed solvent of 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 diluted with water, and neutralized with 1 N hydrochloric acid. 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 to give the title compound (550 mg, yield 75%) as colorless crystals. MS: m/z 585 (MH+), 1H NMR (CDCl3) δ: 2.58-2.67 (2H, m), 2.80-2.94 (6H, m), 5.00 (2H, s), 5.26 (2H, s), 6.46 (1H, s), 6.86 (2H, d, J=8.9 Hz), 7.06-7.14 (6H, m), 7.18-7.32 (3H, m), 7.36 (2H, d, J=8.3 Hz), 7.63 (2H, d, J=8.1 Hz), 7.90 (2H, d, J=8.1 Hz).

Workup

  1. stirringthe mixture was further stirred at room temperature for 1 hr
  2. extractionthe mixture was extracted with ethyl acetate
  3. dry with materialThe ethyl acetate layer was dried
  4. concentrationconcentrated under reduced pressure
  5. customThe residue was purified by silica gel column chromatography (hexane:ethyl acetate=19:1-1:1)
  6. customto give a yellow oil
  7. additionwas added
  8. stirringThe mixture was stirred at room temperature for 1 hr
  9. extractionThe mixture was extracted with ethyl acetate
  10. dry with materialThe ethyl acetate layer was dried
  11. concentrationconcentrated under reduced pressure

Sources & evidence

ORD record
ord-cadbe7a448f5429289c82df29fb546a5
Source dataset
uspto-grants-2009_04
Patent number
US07517910B2

Reaction notes

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