Reaktion #2153748

Reaktionsgleichung

Methyl benzene sulfonate

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

lithium bis(trimethylsilyl)amide

→

title compound

1-(3-Chloro-4-fluorobenzyl)-5,6-dihydropyridin-2(1H)-one

Lösungsmittel

ethyl acetate

tetrahydrofuran

Reaktionsbedingungen

Aufarbeitung

1. 1
   workup.ADDITIONAfter the addition
2. 2
   workup.STIRRINGThe reaction mixture was stirred at −20° C. for 30 minutes
3. 3
   Waschenwashed with water (four times; 2 L each time)
4. 4
   ExtraktionThe organic extract
5. 5
   Einengenwas concentrated under vacuum
6. 6
   workup.DISSOLUTIONThe residue was dissolved in toluene (4 L)
7. 7
   workup.ADDITIONtreated with solid sodium carbonate (500 g)
8. 8
   Temperaturheated at 100° C. for one hour
9. 9
   workup.ADDITIONThe product mixture was diluted with ethyl acetate (4 L)
10. 10
    Waschenwashed with water (4 times; 2 L each)
11. 11
    ExtraktionThe organic extract
12. 12
    Einengenwas concentrated under vacuum
13. 13
    SonstigeCollection and concentration of appropriate fractions

Vorschrift

To a cold (−20° C.) solution of 1-(3-chloro-4-fluorobenzyl)piperidin-2-one (340 g, 1.41 mol) in anhydrous tetrahydrofuran (5 L) under an atmosphere of nitrogen, a solution of lithium bis(trimethylsilyl)amide (3.09 L, 3.09 mol; 1M in THF) was added over a period of 40 minutes with the temperature of the reaction maintained at −20° C. After the addition was complete, the reaction mixture was stirred at −20° C. for one hour. Methyl benzene sulfonate (231 mL, 1.69 mol) was added to the reaction mixture over a period of 30 minutes. The reaction mixture was stirred at −20° C. for 30 minutes. The product mixture was diluted with ethyl acetate (4 L) and washed with water (four times; 2 L each time). The organic extract was concentrated under vacuum. The residue was dissolved in toluene (4 L), treated with solid sodium carbonate (500 g), and heated at 100° C. for one hour. The product mixture was diluted with ethyl acetate (4 L) and washed with water (4 times; 2 L each). The organic extract was concentrated under vacuum. The residue was subjected to column chromatography on silica gel eluting with a gradient of 0-60% EtOAc in heptane. Collection and concentration of appropriate fractions provide the title compound as oil.

Quelle