反応 #48120

反応方程式

4-Fluorobenzenesulfonyl chloride

Sodium hydride

(4,4-difluoro-piperidin-1-yl)-[5-(1-isopropyl-piperidin-4-yloxy)-1H-indol-2-yl]-methanone

(4,4-Difluoro-piperidin-1-yl)-[5-(1-isopropyl-piperidin-4-yloxy)-1H-indol-2-yl]-methanone

intermediate 1

(4,4-Difluoro-piperidin-1-yl)-[5-(1-isopropyl-piperidin-4-yloxy)-1H-indol-2-yl]-methanone

→

desired product

収率 60.1%

(4,4-Difluoro-piperidin-1-yl)-[1-(4-fluoro-benzenesulfonyl)-5-(1-isopropyl-piperidin-4-yloxy)-1H-indol-2-yl]-methanone

収率 60.1%

溶媒

N,N-dimethylformamide

反応条件

後処理

1. 1
   workup.STIRRINGthe reaction mixture was stirred at 70° C. overnight
2. 2
   その他The reaction mixture was partitioned between ethyl acetate and water
3. 3
   抽出The aqueous layer was extracted with ethyl acetate
4. 4
   洗浄the combined organic fractions were washed with water and brine
5. 5
   乾燥dried over sodium sulfate
6. 6
   ろ過filtered
7. 7
   その他evaporated to dryness
8. 8
   その他purified on silica gel
9. 9
   洗浄eluting with dichloromethane/methanol 49:1

実験手順

Sodium hydride (60% dispersion in oil, 24 mg, 1.1 eq.) was added to a mixture of (4,4-difluoro-piperidin-1-yl)-[5-(1-isopropyl-piperidin-4-yloxy)-1H-indol-2-yl]-methanone (intermediate 1, 200 mg, 1.0 eq.) in N,N-dimethylformamide (2 mL) and stirred at 70° C. for 30 min. 4-Fluorobenzenesulfonyl chloride (115 mg, 1.2 eq.) was added and the reaction mixture was stirred at 70° C. overnight. The reaction mixture was partitioned between ethyl acetate and water. The aqueous layer was extracted with ethyl acetate and the combined organic fractions were washed with water and brine, dried over sodium sulfate, filtered, evaporated to dryness and purified on silica gel, eluting with dichloromethane/methanol 49:1 to yield 167 mg (60%) of the desired product as yellow foam. MS (m/e): 564.4 (MH+, 100%).

出典