Water → 2-(6-methoxy-1H-inden-3-yl)propanoic Acid

HRID 1454023Notes

Reaction equation

HRID 1454023 reaction equation
[OH-].[Na+].O.[CH3:4][O:5][C:6]1[CH:14]=[C:13]2[C:9]([C:10]([CH:15]([CH3:20])[C:16]([O:18]C)=[O:17])=[CH:11][CH2:12]2)=[CH:8][CH:7]=1.C1COCC1>CO>[CH3:4][O:5][C:6]1[CH:14]=[C:13]2[C:9]([C:10]([CH:15]([CH3:20])[C:16]([OH:18])=[O:17])=[CH:11][CH2:12]2)=[CH:8][CH:7]=1

Participants

6

Reactant 4

HCID 962WaterHCID 8028TetrahydrofuranHCID 14798Sodium HydroxideHCID 57528968methyl 2-(6-methoxy-1H-inden-3-yl)propanoate

Product 1

HCID 219427692-(6-methoxy-1H-inden-3-yl)propanoic AcidYield 90.3%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Conditions

Temperature
38 °C

Procedure

In a 1 L three-neck flask charged with NaOH (18.57 g, 0.464 mol) and water (216 mL), was slowly added (over 15-20 minutes) a solution of methyl 2-(6-methoxy-1H-inden-3-yl)propanoate (Example 8) (53.92 g, 0.232 mol) in MeOH (215 mL). During the addition, the reaction temperature increased to 38° C. To this mixture was added THF (108 mL), and then the mixture was heated to 40-45° C. for a period of 8 h and subsequently stirred at rt for 17 h. The solvent was removed under vacuum and the resulting aqueous mixture was extracted with CH2Cl2 (3×100 mL). The aqueous layer was acidified with HCl (38 mL, 37% aqueous solution) to pH ˜2.5 and extracted with EtOAc (3×100 mL). The combined organic layers were washed with water (4×150 mL) and brine (50 mL), dried over Na2SO4, and filtered. The solvent was evaporated under vacuum and the resulting oil was dried under vacuum at 40-45° C for 16-18 h to give 45.71 g (90%) of the title compound. 1H NMR (400 MHz, DMSO-d6): δ 7.25 (1H, d), 7.05 (1H, s), 6.83 (1H, dd), 6.19 (1H, s), 3.73 (3H, s), 3.68 (1H, q), 3.30 (2H, s), 1.39 (3H, d); LC-MS: RT=2.43 min, (M+H)+: 219.1.

Workup

  1. additionDuring the addition
  2. temperaturethe mixture was heated to 40-45° C. for a period of 8 h
  3. customThe solvent was removed under vacuum
  4. extractionthe resulting aqueous mixture was extracted with CH2Cl2 (3×100 mL)
  5. extractionextracted with EtOAc (3×100 mL)
  6. washThe combined organic layers were washed with water (4×150 mL) and brine (50 mL)
  7. dry with materialdried over Na2SO4
  8. filtrationfiltered
  9. customThe solvent was evaporated under vacuum
  10. customthe resulting oil was dried under vacuum at 40-45° C for 16-18 h

Sources & evidence

ORD record
ord-d161ed9c92a14c04a47d88806536453b
Source dataset
uspto-grants-2009_01
Patent number
US07476742B2

Reaction notes

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