Hydrochloric Acid → HCID 23159858, compound

HRID 2110901Notes

Reaction equation

HRID 2110901 reaction equation
[CH:1]([C:4]1[CH:8]=[C:7]([C:9]2[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=2)[NH:6][N:5]=1)([CH3:3])[CH3:2].[H-].[Na+].Cl[CH2:18][C:19]1[CH:38]=[CH:37][C:22]([CH2:23][O:24][C:25]2[CH:30]=[CH:29][C:28]([CH2:31][CH2:32][C:33]([O:35]C)=[O:34])=[CH:27][CH:26]=2)=[CH:21][CH:20]=1.Cl>CO.O1CCCC1.[OH-].[Na+].O.CN(C)C=O>[CH:1]([C:4]1[N:5]([CH2:18][C:19]2[CH:38]=[CH:37][C:22]([CH2:23][O:24][C:25]3[CH:30]=[CH:29][C:28]([CH2:31][CH2:32][C:33]([OH:35])=[O:34])=[CH:27][CH:26]=3)=[CH:21][CH:20]=2)[N:6]=[C:7]([C:9]2[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=2)[CH:8]=1)([CH3:3])[CH3:2]

Participants

10

Reactant 4

HCID 313Hydrochloric Acid2×HCID 24758Sodium hydrideHCID 23082857Methyl 3-(4-([4-(chloromethyl)benzyl]oxy)phenyl)propanoateHCID 178438779HCID 178438779, compound

Product 1

HCID 23159858HCID 23159858, compoundYield 56%

Reagents, catalysts & solvents 5

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

Procedure

A mixture of 3-isopropyl-5-phenyl-1H-pyrazole (186 mg, 1.0 mmol), sodium hydride (60% in oil, 40 mg, 1.0 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 for 1 hr. The reaction mixture was poured into 1 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=19:1-1:1) to give a yellow oil. The yellow oil was dissolved in a mixed solvent of methanol (3 mL) and tetrahydrofuran (3 mL), and 1 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, neutralized with 1 N hydrochloric acid, and 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 (254 mg, yield 56%, 2 steps) as a colorless oil.

Workup

  1. stirringthe mixture was further stirred 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. extractionextracted with ethyl acetate
  10. dry with materialThe ethyl acetate layer was dried
  11. concentrationconcentrated under reduced pressure
  12. customThe residue was purified by silica gel column chromatography (hexane:ethyl acetate=9:1-1:4)

Sources & evidence

ORD record
ord-8932b2b57ad04a3d8dc32b13efdcf769
Source dataset
uspto-grants-2009_04
Patent number
US07517910B2

Reaction notes

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