Reaktion #699668

Reaktionsgleichung

2,3-dihydro-4-fluoro-2-(4-pyridinylamino)-1H-isoindol-5-ol hydrobromide

triethylamine

dimethylcarbamyl chloride

sodium bicarbonate

→

product

Ausbeute 69.3%

2,3-Dihydro-4-fluoro-2-(4-pyridinylamino)-1H-isoindol-5-yl dimethylcarbamate hydrochloride

Ausbeute 69.3%

Lösungsmittel

chloroform

chloroform

Reaktionsbedingungen

Aufarbeitung

1. 1
   workup.ADDITIONwas added dropwise
2. 2
   workup.STIRRINGThe reaction mixture was stirred
3. 3
   Temperaturunder reflux for 5 hrs, at ambient temperature overnight
4. 4
   SonstigeThe layers were separated
5. 5
   ExtraktionThe aqueous phase was extracted with chloroform
6. 6
   Trocknenthe combined organic layers were dried over anhydrous magnesium sulfate
7. 7
   Filtrationfiltered
8. 8
   Sonstigethe filtrate was evaporated in vacuo
9. 9
   Sonstigechromatographed (silica)
10. 10
    Wascheneluting with 7% methanol-dichloromethane
11. 11
    SonstigeThe appropriate fractions were collected
12. 12
    Sonstigeevaporated
13. 13
    workup.DISSOLUTIONThe residue was dissolved in absolute ethanol
14. 14
    workup.ADDITIONexcess ethereal hydrogen chloride was added
15. 15
    workup.ADDITIONEther was added
16. 16
    Temperaturthe solution was cooled
17. 17
    SonstigeThe precipitate was collected

Vorschrift

To a mixture of 2,3-dihydro-4-fluoro-2-(4-pyridinylamino)-1H-isoindol-5-ol hydrobromide (600 mg), triethylamine (614 mg), and chloroform (10 ml), dimethylcarbamyl chloride (237 mg) in chloroform (5 ml) was added dropwise, with stirring at ambient temperature, under nitrogen. The reaction mixture was stirred under reflux for 5 hrs, at ambient temperature overnight and poured into dilute sodium bicarbonate solution (100 ml). The layers were separated. The aqueous phase was extracted with chloroform, and the combined organic layers were dried over anhydrous magnesium sulfate, filtered, and the filtrate was evaporated in vacuo. The residue was flash chromatographed (silica), eluting with 7% methanol-dichloromethane followed by 185:14:1 dichloromethane-methanol-ammonium hydroxide. The appropriate fractions were collected and evaporated. The residue was dissolved in absolute ethanol and excess ethereal hydrogen chloride was added. Ether was added and the solution was cooled. The precipitate was collected to give 450 mg (69%) of product, mp 250-252° C. (dec).

Quelle