Reaktion #8183

Reaktionsgleichung

Pyridine hydrochloride

4-methoxy-3,3-dimethyl-1,3-dihydro-indol-2-one

→

4-hydroxy-3,3-dimethyl-1,3-dihydro-indol-2-one

Ausbeute 68.9%

Lösungsmittel

hexane

Reaktionsbedingungen

Aufarbeitung

1. 1
   TemperaturHeating
2. 2
   Sonstigeis removed
3. 3
   Temperaturwhen the mixture cooled to 100° C.
4. 4
   workup.ADDITIONwater (60 mL) is added
5. 5
   Sonstigefollowed by ethyl acetate (150 mL) at 65° C
6. 6
   SonstigeThe layers are separated
7. 7
   Extraktionthe aqueous phase is extracted five times with ethyl acetate (50 mL)
8. 8
   ExtraktionThe combined organic layers are extracted first with a combination of aqueous hydrochloric acid (1N, 10 mL)
9. 9
   TrocknenAfter drying over magnesium sulfate
10. 10
    Sonstigethe solvent is removed via rotary evaporation
11. 11
    workup.DISSOLUTIONThe crude material is dissolved in ethyl acetate (200 mL)
12. 12
    Sonstigeat 60° C
13. 13
    SonstigeCrystallization
14. 14
    workup.WAITto begin slowly over 1 hour at 50° C
15. 15
    workup.STIRRINGAfter stirring for 12 hours at 24° C.
16. 16
    Temperaturthe slurry is cooled to 0° C. for 1 hour
17. 17
    Filtrationvacuum filtered
18. 18
    Waschenwashing twice with cold 1:1, ethyl acetate

Vorschrift

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%.

Quelle