Réaction #48120

Équation de réaction

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

Rendement 60.1%

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

Rendement 60.1%

Solvants

N,N-dimethylformamide

Conditions de réaction

Traitement

1. 1
   workup.STIRRINGthe reaction mixture was stirred at 70° C. overnight
2. 2
   AutreThe reaction mixture was partitioned between ethyl acetate and water
3. 3
   ExtractionThe aqueous layer was extracted with ethyl acetate
4. 4
   Lavagethe combined organic fractions were washed with water and brine
5. 5
   Séchagedried over sodium sulfate
6. 6
   Filtrationfiltered
7. 7
   Autreevaporated to dryness
8. 8
   Autrepurified on silica gel
9. 9
   Lavageeluting with dichloromethane/methanol 49:1

Mode opératoire

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%).

Source