Potassium Hydroxide → 2-(6-methoxy-1H-inden-3-yl)butanoic acid

HRID 46017Notes

Reaction equation

HRID 46017 reaction equation
[CH3:1][O:2][C:3]1[CH:11]=[C:10]2[C:6]([C:7]([CH:12]([CH2:17][CH3:18])[C:13]([O:15]C)=[O:14])=[CH:8][CH2:9]2)=[CH:5][CH:4]=1.[OH-].[K+]>CO.O>[CH3:1][O:2][C:3]1[CH:11]=[C:10]2[C:6]([C:7]([CH:12]([CH2:17][CH3:18])[C:13]([OH:15])=[O:14])=[CH:8][CH2:9]2)=[CH:5][CH:4]=1

Participants

5

Reactant 2

HCID 14797Potassium Hydroxide2×HCID 11402344Methyl 2-(6-methoxy-1H-inden-3-yl)butanoate

Product 1

HCID 112532602-(6-methoxy-1H-inden-3-yl)butanoic acidYield 95%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 962WaterSolvent2×

Conditions

Temperature
60 °C

Procedure

To a solution of the ester prepared in Example 1 (14.0 g, 58.9 mmol) in 140 mL MeOH, was added a solution of KOH (6.4 g, 113.8 mmol) in 5 mL water. The reaction mixture was stirred at 60° C. (pot temperature) for 2 hours. TLC showed 70% conversion. A solution of KOH (3.0 g, 53.6 mmol) in 100 mL water was then slowly added to the pot. After 1 hour, the reaction was completed. After cooling to room temperature, the solvents were removed at a reduced pressure. The residue was dissolved in 500 mL water, and then washed with EtOAc. The aqueous layer was cooled in an ice-water bath, and then acidified with conc. HCl to pH<3.0. The product was extracted into 300 mL CH2Cl2, washed with water (2×100 mL), then dried over Na2SO4. After Na2SO4 was filtered off, the CH2Cl2 solution was stirred with 3.0 g of charcoal for 2 hours. The charcoal was removed by filtration through a pad of Celite®. The title product (12.5 g, 95%) was obtained as a light brown solid after solvent removal and vacuum drying. 1H NMR (DMSO-d6) δ12.20 (b, 1H), 7.30 (d, 1H), 7.06 (d, 1H), 6.82 (dd, 1H), 6.22 (s, 1H), 3.75 (s, 3H), 3.45 (t, 1H), 3.30 (s, 2H), 1.90 (m, 1H), 1.78 (m, 1H), 0.90 (t, 3H).

Workup

  1. waitAfter 1 hour
  2. temperatureAfter cooling to room temperature
  3. customthe solvents were removed at a reduced pressure
  4. dissolutionThe residue was dissolved in 500 mL water
  5. washwashed with EtOAc
  6. temperatureThe aqueous layer was cooled in an ice-water bath
  7. extractionThe product was extracted into 300 mL CH2Cl2
  8. washwashed with water (2×100 mL)
  9. dry with materialdried over Na2SO4
  10. filtrationAfter Na2SO4 was filtered off
  11. stirringthe CH2Cl2 solution was stirred with 3.0 g of charcoal for 2 hours
  12. customThe charcoal was removed by filtration through a pad of Celite®

Sources & evidence

ORD record
ord-d49ccf97e6864396baf2290a52f62d38
Source dataset
uspto-grants-2013_09
Patent number
US08541618B2

Reaction notes

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