Water → HCID 59314229, compound

HRID 1047851Notes

Reaction equation

HRID 1047851 reaction equation
C[O:2][C:3]([C:5]1([NH:14][C:15]([C:17]2[C:18]3[CH2:19][CH2:20][C:21]([CH3:31])([CH3:30])[C:22]=3[CH:23]=[C:24]([C:26]([CH3:29])([CH3:28])[CH3:27])[CH:25]=2)=[O:16])[CH2:13][C:12]2[C:7](=[CH:8][CH:9]=[CH:10][CH:11]=2)[CH2:6]1)=[O:4].[OH-].[K+].O>CCO>[C:26]([C:24]1[CH:25]=[C:17]([C:15]([NH:14][C:5]2([C:3]([OH:4])=[O:2])[CH2:6][C:7]3[C:12](=[CH:11][CH:10]=[CH:9][CH:8]=3)[CH2:13]2)=[O:16])[C:18]2[CH2:19][CH2:20][C:21]([CH3:31])([CH3:30])[C:22]=2[CH:23]=1)([CH3:27])([CH3:28])[CH3:29]

Participants

5

Reactant 3

HCID 962WaterHCID 14797Potassium HydroxideHCID 59314084HCID 59314084, compound

Product 1

HCID 59314229HCID 59314229, compoundYield 80%

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Procedure

A mixture of 2-[(6-tert-butyl-1,1-dimethyl-indane-4-carbonyl)-amino]-indan-2-carboxylic acid methyl ester (600 mg, 1.4 mmol) and KOH (1.8 g, 30.8 mmol) is dissolved in EtOH (25 mL) and water (2 mL) under water bath. The water bath is removed when KOH is completely dissolved and the resulting reaction solution is stirred at RT for 8 h. After concentration in vacuo, the residue is neutralized with 1N HCl and extracted with EtOAc (3×150 mL), the organic washes are combined and concentrated in vacuo. The residue is purified by preparative HPLC (C18 column 10 micron, gradient elution: 20-100% ACN 0.1% TFA in H2O 0.1% TFA). Product crystallizes out of the collected fractions on standing. Filtration and drying gave pure product as white solid (454 mg, 78%).

Workup

  1. customThe water bath is removed when KOH
  2. dissolutionis completely dissolved
  3. customthe resulting reaction solution
  4. concentrationAfter concentration in vacuo
  5. extractionextracted with EtOAc (3×150 mL)
  6. concentrationconcentrated in vacuo
  7. customThe residue is purified by preparative HPLC (C18 column 10 micron, gradient elution: 20-100% ACN 0.1% TFA in H2O 0.1% TFA)
  8. customProduct crystallizes out of the collected fractions
  9. filtrationFiltration
  10. customdrying

Sources & evidence

ORD record
ord-3a9af32eb5b74c05b84b4446d4d01cf6
Source dataset
uspto-grants-2013_10
Patent number
US08569535B2

Reaction notes

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