反応 #8197

反応方程式

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

収率 58.0%

溶媒

dimethylformamide

反応条件

後処理

1. 1
   温度the mixture is heated in an oil bath to eighty degrees Celsius for 15 hours, under nitrogen
2. 2
   温度The mixture is then heated an additional 5 hours at eighty-five degrees Celsius
3. 3
   その他to quench
4. 4
   その他the reaction
5. 5
   抽出the mixture is extracted three times with 50 mL of ethyl acetate
6. 6
   洗浄washed twice with 50 mL of 1.00 N sodium hydroxide
7. 7
   乾燥The organic layer is dried with sodium sulfate
8. 8
   ろ過filtered
9. 9
   その他the solvent evaporated
10. 10
    workup.DISSOLUTIONThe residue is dissolved in dichloromethane
11. 11
    その他purified

実験手順

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).

出典