Reaktion #57441

Reaktionsgleichung

2-(tetrahydro-2H-pyran-4-yloxy)-1H-isoindole-1,3(2H)-dione

hydrazine

4-methoxybenzenesulfonyl chloride

diisopropylethylamine

→

white solid

Ausbeute 30.0%

N-(tetrahydro-2H-pyran-4-yloxy)-4-methoxy-1-benzenesulfonamide

Ausbeute 30.0%

Lösungsmittel

THF

Reaktionsbedingungen

Aufarbeitung

1. 1
   SonstigeThe reaction
2. 2
   Sonstigeimmediately formed a white suspension
3. 3
   FiltrationThe suspension was filtered directly into a flask
4. 4
   workup.ADDITIONwas added
5. 5
   workup.STIRRINGAfter stirring at room temperature for 15 hours
6. 6
   Temperaturthe reaction was refluxed for 4 hours
7. 7
   workup.STIRRINGstirred at room temperature for 12 days
8. 8
   Einengenconcentrated to a yellow solid
9. 9
   SonstigeThe resulting solid was partitioned between ethyl acetate and 1N HCl
10. 10
    Sonstigethe organic layer was separated
11. 11
    Waschenwashed with a saturated aqueous solution of sodium bicarbonate and brine
12. 12
    Trocknendried over magnesium sulfate
13. 13
    EinengenThe crude product was concentrated to a white solid
14. 14
    Sonstigepurified by silica gel chromatography (1:1 hexanes/ethyl acetate) and crystallization (hexanes/ethyl acetate)

Vorschrift

2-(tetrahydro-2H-pyran-4-yloxy)-1H-isoindole-1,3(2H)-dione (6.8 mmol, 1.69 g) was combined with hydrazine (6.8 mmol, 0.22 mL) in anhydrous THF (20 mL) under nitrogen. The reaction immediately formed a white suspension and was allowed to stir at room temperature for 1 hour. The suspension was filtered directly into a flask containing 4-methoxybenzenesulfonyl chloride (6.5 mmol, 1.34 g) and diisopropylethylamine (20.5 mmol, 3.6 mL) was added. After stirring at room temperature for 15 hours, the reaction was refluxed for 4 hours, then stirred at room temperature for 12 days and concentrated to a yellow solid. The resulting solid was partitioned between ethyl acetate and 1N HCl, and the organic layer was separated and washed with a saturated aqueous solution of sodium bicarbonate and brine, and dried over magnesium sulfate. The crude product was concentrated to a white solid and purified by silica gel chromatography (1:1 hexanes/ethyl acetate) and crystallization (hexanes/ethyl acetate) providing 0.554 g (30%) of a white solid. Rf=0.4 (1:1 hexanes/ethyl acetate); H1-NMR (CDCl3): δ 7.83(2H,d), 7.00 (2H,d), 6.72 (1H,s), 4.23-4.11 (1H,m), 3.91-3.81 (2H,m), 3.87 (3H,s), 3.46-3.38 (2H,m), 2.03-1.94 (2H,m), 1.63-1.51 (2H,m).

Quelle