Reaktion #1904507

Reaktionsgleichung

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

LHMDS

methyl benzene sulfonate

→

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

Lösungsmittel

THF

EtOAc

Reaktionsbedingungen

Aufarbeitung

1. 1
   Sonstigeat −20° C.
2. 2
   Sonstigeat −20° C
3. 3
   workup.WAITThe reaction was aged for 30 minutes at −20° C.
4. 4
   Waschenwashed with four 2 L portions of distilled H2O
5. 5
   EinengenThe organic layer was concentrated
6. 6
   workup.DISSOLUTIONthe residue was dissolved in 4 L toluene
7. 7
   workup.ADDITIONNa2CO3 (500 g) was added
8. 8
   Temperaturthe reaction heated to 100° C. for 1 hour
9. 9
   workup.ADDITIONThe residue was diluted with 4 L EtOAc
10. 10
    Waschenwashed with four 2 L portions of distilled water
11. 11
    EinengenThe organic layer was concentrated
12. 12
    Sonstigethe residue purified by flash chromatography on silica eluting with a gradient of 0-60% EtOAc/heptane
13. 13
    SonstigeThe product was isolated as an oil

Vorschrift

1-(3-Chloro-4-fluorobenzyl)piperidin-2-one (340 g, 1.41 mol) was dissolved in THF (5 L) and cooled to −20° C. under nitrogen. LHMDS (3.09 L, 3.09 mol, 1M in THF) was added over 40 minutes keeping the temperature at −20° C. and aged for 1 hr at −20° C. The methyl benzene sulfonate (231 mL, 1.69 mol) was added over 30 minutes, again keeping the internal temperature at −20° C. The reaction was aged for 30 minutes at −20° C. and LCMS showed the reaction complete. The reaction mixture was diluted with 4 L EtOAc and washed with four 2 L portions of distilled H2O. The organic layer was concentrated and the residue was dissolved in 4 L toluene. Na2CO3 (500 g) was added and the reaction heated to 100° C. for 1 hour. LCMS showed the reaction complete. The residue was diluted with 4 L EtOAc and washed with four 2 L portions of distilled water. The organic layer was concentrated and the residue purified by flash chromatography on silica eluting with a gradient of 0-60% EtOAc/heptane. The product was isolated as an oil.

Quelle