4-Methoxy-3,3-dimethyl-1,3-dihydro-indol-2-one → 4-Hydroxy-3,3-dimethyl-1,3-dihydro-indol-2-one

HRID 8087Notes

Reaction equation

HRID 8087 reaction equation
Cl.N1C=CC=CC=1.C[O:9][C:10]1[CH:18]=[CH:17][CH:16]=[C:15]2[C:11]=1[C:12]([CH3:21])([CH3:20])[C:13](=[O:19])[NH:14]2>CCCCCC>[OH:9][C:10]1[CH:18]=[CH:17][CH:16]=[C:15]2[C:11]=1[C:12]([CH3:21])([CH3:20])[C:13](=[O:19])[NH:14]2

Participants

4

Reactant 2

HCID 6007074-Methoxy-3,3-dimethyl-1,3-dihydro-indol-2-oneHCID 10176127Pyridinium chloride

Product 1

HCID 5957464-Hydroxy-3,3-dimethyl-1,3-dihydro-indol-2-oneYield 68.9%

Reagents, catalysts & solvents 1

HCID 8058HexaneSolvent

Conditions

Temperature
220 °C

Procedure

Pyridine hydrochloride (51.10 g, 442.2 mmol) and 4-methoxy-3,3-dimethyl-1,3-dihydro-indol-2-one (21.61 g, 113.0 mmol) are combined and stirred in a melt at 220° C. for 45 minutes. Heating is removed and when the mixture cooled to 100° C., water (60 mL) is added, followed by ethyl acetate (150 mL) at 65° C. The layers are separated and the aqueous phase is extracted five times with ethyl acetate (50 mL). The combined organic layers are extracted first with a combination of aqueous hydrochloric acid (1N, 10 mL) and a saturated solution of sodium chloride (10 mL), then with a combination of a saturated solution of sodium bicarbonate (10 mL) and a saturated solution of sodium chloride (10 mL). After drying over magnesium sulfate, the solvent is removed via rotary evaporation. The crude material is dissolved in ethyl acetate (200 mL) and hexane (200 mL) at 60° C. Crystallization is allowed to begin slowly over 1 hour at 50° C. After stirring for 12 hours at 24° C., the slurry is cooled to 0° C. for 1 hour, then vacuum filtered washing twice with cold 1:1, ethyl acetate:hexane (35 mL, 0° C.) to provide 13.8 g (98.6% purity, 68% yield) of 4-hydroxy-3,3-dimethyl-1,3-dihydro-indol-2-one, mp 224–225° C. MS (ES+) m/z 178 (M++1). From the filtrate a second crop (5.0 g, 98.4% purity, 25% yield) is obtained to give a total yield of 93%.

Workup

  1. temperatureHeating
  2. customis removed
  3. temperaturewhen the mixture cooled to 100° C.
  4. additionwater (60 mL) is added
  5. customfollowed by ethyl acetate (150 mL) at 65° C
  6. customThe layers are separated
  7. extractionthe aqueous phase is extracted five times with ethyl acetate (50 mL)
  8. extractionThe combined organic layers are extracted first with a combination of aqueous hydrochloric acid (1N, 10 mL)
  9. dry with materialAfter drying over magnesium sulfate
  10. customthe solvent is removed via rotary evaporation
  11. dissolutionThe crude material is dissolved in ethyl acetate (200 mL)
  12. customat 60° C
  13. customCrystallization
  14. waitto begin slowly over 1 hour at 50° C
  15. stirringAfter stirring for 12 hours at 24° C.
  16. temperaturethe slurry is cooled to 0° C. for 1 hour
  17. filtrationvacuum filtered
  18. washwashing twice with cold 1:1, ethyl acetate

Sources & evidence

ORD record
ord-6e6691a549f845a5a05326a4086fecbe
Source dataset
uspto-grants-2006_08
Patent number
US07087635B2

Reaction notes

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