Hydrochloric Acid → 4-[2-({[4-(2-tert-Butylphenyl)piperazin-1-yl](oxo)acetyl}amino)ethyl]benzoic acid

HRID 534995Notes

Reaction equation

HRID 534995 reaction equation
[C:1]([C:5]1[CH:10]=[CH:9][CH:8]=[CH:7][C:6]=1[N:11]1[CH2:16][CH2:15][N:14]([C:17](=[O:33])[C:18]([NH:20][CH2:21][CH2:22][C:23]2[CH:32]=[CH:31][C:26]([C:27]([O:29]C)=[O:28])=[CH:25][CH:24]=2)=[O:19])[CH2:13][CH2:12]1)([CH3:4])([CH3:3])[CH3:2].[Li+].[OH-].[OH-].[Na+].Cl>O1CCCC1.CO>[C:1]([C:5]1[CH:10]=[CH:9][CH:8]=[CH:7][C:6]=1[N:11]1[CH2:12][CH2:13][N:14]([C:17](=[O:33])[C:18]([NH:20][CH2:21][CH2:22][C:23]2[CH:24]=[CH:25][C:26]([C:27]([OH:29])=[O:28])=[CH:31][CH:32]=2)=[O:19])[CH2:15][CH2:16]1)([CH3:4])([CH3:2])[CH3:3]

Participants

7

Reactant 4

HCID 313Hydrochloric AcidHCID 3939Lithium HydroxideHCID 14798Sodium HydroxideHCID 66750860Methyl 4-[2-({[4-(2-tert-butylphenyl)piperazin-1-yl](oxo)acetyl}amino)ethyl]benzoate

Product 1

HCID 667927434-[2-({[4-(2-tert-Butylphenyl)piperazin-1-yl](oxo)acetyl}amino)ethyl]benzoic acidYield 8%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 8028TetrahydrofuranSolvent

Procedure

A mixture of methyl 4-[2-({[4-(2-tert-butylphenyl)piperazin-1-yl](oxo)acetyl}amino)ethyl]benzoate (Example 202, 0.51 g, 1.13 mmol) and 1 M LiOH solution (5 mL, 5.0 mmol) in tetrahydrofuran (5 mL) was stirred at room temperature for 1 h. Then to this mixture was added 8 M NaOH solution (5 mL, 40 mmol) and methanol (10 mL) and stirred at room temperature for 2 h. The reaction mixture was acidified with 1 M HCl solution and extracted with ethyl acetate. The extract was washed with brine, dried over anhydrous magnesium sulfate, filtered and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (hexane/ethyl acetate 70:30 to 0:100 then ethyl acetate/methanol 100/0 to 70/30) and HPLC (Gilson Preparative HPLC System; column: YMC Combiprep ODS-A, S-5 μm, 50×20 mm; solvent: A; water containing 0.1% TFA, B; acetonitrile containing 0.1% TFA; gradient cycle: 0.00 min (A/B=90/10), 1.00 min (A/B=90/10), 4.20 min (A/B=10/90), 5.40 min (A/B=10/90), 5.50 min (A/B=90/10), 5.60 min (A/B=90/10); flow rate: 25 mL/min; detect: UV 220 nm) to give the title compound (38 mg, 8%) as a yellow amorphous.

Workup

  1. stirringstirred at room temperature for 2 h
  2. extractionextracted with ethyl acetate
  3. washThe extract was washed with brine
  4. dry with materialdried over anhydrous magnesium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated under reduced pressure
  7. customThe residue was purified by silica gel column chromatography (hexane/ethyl acetate 70:30 to 0:100
  8. custom0.00 min
  9. custom1.00 min
  10. custom4.20 min
  11. custom5.40 min
  12. custom5.50 min
  13. custom5.60 min

Sources & evidence

ORD record
ord-01ff195718c84854b8679dbb19fa2d33
Source dataset
uspto-grants-2014_10
Patent number
US08853215B2

Reaction notes

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