Water → 2-[4-[2-(benzoxazol-2-ylthio)ethyl]piperazin-1-yl]-N-(2,6-diisopropyl-3-hydroxyphenyl)acetamide

HRID 1064806Notes

Reaction equation

HRID 1064806 reaction equation
[O:1]1[C:5]2[CH:6]=[CH:7][CH:8]=[CH:9][C:4]=2[N:3]=[C:2]1[S:10][CH2:11][CH2:12][N:13]1[CH2:18][CH2:17][N:16]([CH2:19][C:20]([NH:22][C:23]2[C:28]([CH:29]([CH3:31])[CH3:30])=[CH:27][CH:26]=[C:25](N)[C:24]=2[CH:33]([CH3:35])[CH3:34])=[O:21])[CH2:15][CH2:14]1.N([O-])=[O:37].[Na+].O.C(=O)(O)[O-].[Na+]>S(=O)(=O)(O)O>[O:1]1[C:5]2[CH:6]=[CH:7][CH:8]=[CH:9][C:4]=2[N:3]=[C:2]1[S:10][CH2:11][CH2:12][N:13]1[CH2:14][CH2:15][N:16]([CH2:19][C:20]([NH:22][C:23]2[C:28]([CH:29]([CH3:31])[CH3:30])=[CH:27][CH:26]=[C:25]([OH:37])[C:24]=2[CH:33]([CH3:35])[CH3:34])=[O:21])[CH2:17][CH2:18]1

Participants

6

Reactant 4

HCID 962WaterHCID 516892Sodium BicarbonateHCID 222725872-[4-[2-(Benzoxazol-2-ylthio)ethyl]piperazin-1-yl]-N-(3-amino-2,6-diisopropylphenyl)acetamideHCID 23668193Sodium Nitrite

Product 1

HCID 222726162-[4-[2-(benzoxazol-2-ylthio)ethyl]piperazin-1-yl]-N-(2,6-diisopropyl-3-hydroxyphenyl)acetamideYield 89.6%

Reagents, catalysts & solvents 1

HCID 1118Sulfuric AcidSolvent

Conditions

Temperature
0 °C

Procedure

2-[4-[2-(Benzoxazol-2-ylthio)ethyl]piperazin-1-yl]-N-(3-amino-2,6-diisopropylphenyl)acetamide (198 mg, 0.4 mmol) was dissolved in 6% aqueous solution of sulfuric acid (3.4 ml), an aqueous solution (0.8 ml) of sodium nitrite (35 mg, 0.5 mmol) was added thereto at 0° C. and the mixture was stirred at that temperature for 30 minutes. The reaction solution was slowly dropped into a boiling water (40 ml) which was heating and stirring at an external temperature of 140° C. After 10 minutes from the dropping, the reaction solution was allowed to cool, neutralized with sodium bicarbonate and extracted with chloroform. The organic layer was washed with water and a saturated sodium chloride solution successively and dried over anhydrous magnesium sulfate and the solvent was evaporated. The residue was purified by a preparative thin layer chromatography (developing solvent, chloroform:ammonia-saturated methanol=20:1) to provide 178 mg (yield 89%) of the desired compound, which was recrystallized from ethanol-hexane to provide colorless needles.

Workup

  1. temperaturewas heating
  2. stirringstirring at an external temperature of 140° C
  3. waitAfter 10 minutes from the dropping
  4. temperatureto cool
  5. extractionextracted with chloroform
  6. washThe organic layer was washed with water
  7. dry with materiala saturated sodium chloride solution successively and dried over anhydrous magnesium sulfate
  8. customthe solvent was evaporated
  9. customThe residue was purified by a preparative thin layer chromatography (developing solvent, chloroform:ammonia-saturated methanol=20:1)

Sources & evidence

ORD record
ord-8238907d1c694098a4c13dbb6572d58c
Source dataset
uspto-grants-2005_11
Patent number
US06969711B2

Reaction notes

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