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

HRID 1817325Notes

Reaction equation

HRID 1817325 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]([CH:13]=[CH:14][C:15]=1[F:16])[CH2:5][N:6]1[CH2:11][CH2:10][CH2:9][CH2:8][C:7]1=[O:12].[Li+].C[Si]([N-][Si](C)(C)C)(C)C.C1(S(OC)(=O)=O)C=CC=CC=1>C1COCC1.CCOC(C)=O>[Cl:1][C:2]1[CH:3]=[C:4]([CH:13]=[CH:14][C:15]=1[F:16])[CH2:5][N:6]1[CH2:11][CH2:10][CH:9]=[CH:8][C:7]1=[O:12]

Participants

6

Reactant 3

HCID 6630Methyl benzenesulfonateHCID 2733832Lithium HexamethyldisilazideHCID 669976831-(3-Chloro-4-fluorobenzyl)piperidin-2-one

Product 1

HCID 594556041-(3-Chloro-4-fluorobenzyl)-5,6-dihydropyridin-2(1H)-one

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
-20 °C

Procedure

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.

Workup

  1. customat −20° C.
  2. customat −20° C
  3. waitThe reaction was aged for 30 minutes at −20° C.
  4. washwashed with four 2 L portions of distilled H2O
  5. concentrationThe organic layer was concentrated
  6. dissolutionthe residue was dissolved in 4 L toluene
  7. additionNa2CO3 (500 g) was added
  8. temperaturethe reaction heated to 100° C. for 1 hour
  9. additionThe residue was diluted with 4 L EtOAc
  10. washwashed with four 2 L portions of distilled water
  11. concentrationThe organic layer was concentrated
  12. customthe residue purified by flash chromatography on silica eluting with a gradient of 0-60% EtOAc/heptane
  13. customThe product was isolated as an oil

Sources & evidence

ORD record
ord-f988d46e42e7443bb020fc77f87a8632
Source dataset
uspto-grants-2009_10
Patent number
US07598264B2

Reaction notes

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