Reaktion #8197

Reaktionsgleichung

Water

6-Chloro-nicotinic acid methyl ester

[2-(7-hydroxy-1H-indol-3-yl)-1,1-dimethyl-ethyl]-carbamic acid tert-butyl ester

sodium hydride

→

6-[3-(2-tert-butoxycarbonylamino-2-methyl-propyl)-1H-indol-7-yloxy]-nicotinic acid methyl ester

Ausbeute 58.0%

Lösungsmittel

dimethylformamide

Reaktionsbedingungen

Aufarbeitung

1. 1
   Temperaturthe mixture is heated in an oil bath to eighty degrees Celsius for 15 hours, under nitrogen
2. 2
   TemperaturThe mixture is then heated an additional 5 hours at eighty-five degrees Celsius
3. 3
   Sonstigeto quench
4. 4
   Sonstigethe reaction
5. 5
   Extraktionthe mixture is extracted three times with 50 mL of ethyl acetate
6. 6
   Waschenwashed twice with 50 mL of 1.00 N sodium hydroxide
7. 7
   TrocknenThe organic layer is dried with sodium sulfate
8. 8
   Filtrationfiltered
9. 9
   Sonstigethe solvent evaporated
10. 10
    workup.DISSOLUTIONThe residue is dissolved in dichloromethane
11. 11
    Sonstigepurified

Vorschrift

To a solution of [2-(7-hydroxy-1H-indol-3-yl)-1,1-dimethyl-ethyl]-carbamic acid tert-butyl ester (104 mg, 0.342 mmol) in dimethylformamide (10 mL) is added sodium hydride (10 mg, 0.410 mmol). The mixture is stirred at ambient temperature for 30 minutes under nitrogen. 6-Chloro-nicotinic acid methyl ester (99 mg, 0.581 mmol) is added and the mixture is heated in an oil bath to eighty degrees Celsius for 15 hours, under nitrogen. The mixture is then heated an additional 5 hours at eighty-five degrees Celsius. Water (100 ml) is added to quench the reaction and the mixture is extracted three times with 50 mL of ethyl acetate. The organic layers are combined and washed twice with 50 mL of 1.00 N sodium hydroxide. The organic layer is dried with sodium sulfate, filtered and the solvent evaporated. The residue is dissolved in dichloromethane and purified using silica gel chromatography (6% 2M ammonia in methanol, 94% dichloromethane used as mobile phase) to give 87 mg (58%) of 6-[3-(2-tert-butoxycarbonylamino-2-methyl-propyl)-1H-indol-7-yloxy]-nicotinic acid methyl ester. FDMS m/e=440 (M++1).

Quelle