Réaction #46261

Équation de réaction

3-chloro-4-fluorobenzylbromide

valerolactam

sodium hydride

→

title product

1-(3-Chloro-4-fluorobenzyl)piperidin-2-one

Solvants

1-methyl-2-pyrrolidinone

1-methyl-2-pyrrolidinone

Conditions de réaction

Traitement

1. 1
   workup.STIRRINGThe reaction mixture was stirred at 0° C. for 1 hour
2. 2
   Températureto warm up
3. 3
   workup.STIRRINGstirred at room temperature overnight
4. 4
   AutreThe reaction mixture was quenched with distilled water (5 L)
5. 5
   Extractionextracted with dichloromethane (three times; 2 L, 1 L, 1 L)
6. 6
   Lavagewashed with water (3×; 4 L each time)
7. 7
   workup.DISSOLUTIONThe residual oil was dissolved in ethyl acetate (4 L)
8. 8
   Extractionextracted with water (3×; 2 L each time)
9. 9
   AutreThe organic layer was separated
10. 10
    Concentrationconcentrated under vacuum

Mode opératoire

To a cold (0° C.) solution of valerolactam (153.30 g, 1.54 mol) in anhydrous 1-methyl-2-pyrrolidinone (3.5 L), sodium hydride (67.7 g, 1.69 mol, 60% dispersion in oil) was added over a period of 5 minutes. The reaction mixture was stirred for 30 minutes, and a solution of 3-chloro-4-fluorobenzylbromide (345.5 g, 1.54 mol) in 1-methyl-2-pyrrolidinone (200 mL) was added over 30 minutes at 0° C. The reaction mixture was stirred at 0° C. for 1 hour, and was allowed to warm up and stirred at room temperature overnight. The reaction mixture was quenched with distilled water (5 L), and extracted with dichloromethane (three times; 2 L, 1 L, 1 L). The organic extracts were combined, washed with water (3×; 4 L each time). The residual oil was dissolved in ethyl acetate (4 L), and extracted with water (3×; 2 L each time). The organic layer was separated, concentrated under vacuum to give the title product that solidified upon standing.

Source