Potassium Hydroxide → 4-[1-(1,3-Benzodioxol-5-yl)-2-oxo-2-[(4-propan-2-ylphenyl)sulfonylamino]ethoxy]-3-propylbenzoic acid

HRID 744189Notes

Reaction equation

HRID 744189 reaction equation
[K].[CH:2]([C:5]1[CH:10]=[CH:9][C:8]([S:11]([NH:14][C:15](=[O:40])[CH:16]([C:31]2[CH:36]=[CH:35][C:34]3[O:37][CH2:38][O:39][C:33]=3[CH:32]=2)[O:17][C:18]2[CH:23]=[CH:22][C:21]([C:24]([O:26]C)=[O:25])=[CH:20][C:19]=2[CH2:28][CH2:29][CH3:30])(=[O:13])=[O:12])=[CH:7][CH:6]=1)([CH3:4])[CH3:3].[OH-].[K+].C(Cl)Cl.CO.[NH4+].[OH-]>CO.O>[CH:2]([C:5]1[CH:6]=[CH:7][C:8]([S:11]([NH:14][C:15](=[O:40])[CH:16]([C:31]2[CH:36]=[CH:35][C:34]3[O:37][CH2:38][O:39][C:33]=3[CH:32]=2)[O:17][C:18]2[CH:23]=[CH:22][C:21]([C:24]([OH:26])=[O:25])=[CH:20][C:19]=2[CH2:28][CH2:29][CH3:30])(=[O:12])=[O:13])=[CH:9][CH:10]=1)([CH3:3])[CH3:4]

Participants

6

Reactant 3

HCID 14797Potassium HydroxideHCID 21896990Dichloromethane methanol ammonium hydroxideHCID 86749852N-(4-iso-propylbenzenesulfonyl)-alpha-(4-carbomethoxy-2-n-propylphenoxy)-3,4-methylenedioxyphenylacetamide potassium salt

Product 1

HCID 98944604-[1-(1,3-Benzodioxol-5-yl)-2-oxo-2-[(4-propan-2-ylphenyl)sulfonylamino]ethoxy]-3-propylbenzoic acidYield 91.3%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 962WaterSolvent

Conditions

Temperature
60 °C

Procedure

A mixture of 205 g (0.345 mol) of the product of Example 6, 425 mL of 1.0N KOH in methanol and 500 mL of water was stirred at 60° C. under a nitrogen atmosphere. After 1.75 hours TLC analysis (90:10:1 CH2Cl2 -MeOH-NH4OH) indicated that ester hydrolysis was complete. The reaction mixture was cooled slightly, then concentrated on a rotary evaporator. The concentrate was acidified with 400 mL of 2N HCl and extracted first with 6 L of ether-EtOAc-CH2Cl2 4:1:1, then with 3 L of 1:2 EtOAc-CH2Cl2. The organic layers were washed with 250 mL of 2N HCl, then with 3×500 mL of water, dried with magnesium sulfate, filtered, and concentrated, during which, the product began to crystallize. The solution was concentrated to a white sluury of ca. 750 mL, diluted with 1 L of hexanes, cooled to 0° C., aged 1 hr then filtered. The product was air dried affording 170.0 g (91% yield) of the title compound as a white crystalline solid.

Workup

  1. temperatureThe reaction mixture was cooled slightly
  2. concentrationconcentrated on a rotary evaporator
  3. extractionextracted first with 6 L of ether-EtOAc-CH2Cl2 4:1:1
  4. washThe organic layers were washed with 250 mL of 2N HCl
  5. dry with materialwith 3×500 mL of water, dried with magnesium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated, during which
  8. customto crystallize
  9. concentrationThe solution was concentrated to a white sluury of ca. 750 mL
  10. additiondiluted with 1 L of hexanes
  11. temperaturecooled to 0° C., aged 1 hr
  12. filtrationthen filtered
  13. customdried

Sources & evidence

ORD record
ord-279fe8c1932743548f2b0e901168ded8
Source dataset
uspto-grants-1996_09
Patent number
US05559135

Reaction notes

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