Potassium Cyanide → 1-(3-Chloro-4-fluorobenzyl)-4-cyano-5,6-dihydropyridin-2(1H)-one

HRID 1436888Notes

Reaction equation

HRID 1436888 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][CH:9]=[CH:8][C:7]1=[O:12].[C-:17]#[N:18].[K+]>CN(C=O)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][C:9]([C:17]#[N:18])=[CH:8][C:7]1=[O:12]

Participants

5

Reactant 2

HCID 9032Potassium CyanideHCID 594556041-(3-Chloro-4-fluorobenzyl)-5,6-dihydropyridin-2(1H)-one

Product 1

HCID 690645861-(3-Chloro-4-fluorobenzyl)-4-cyano-5,6-dihydropyridin-2(1H)-one

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Conditions

Temperature
90 °C

Procedure

A suspension of 1-(3-chloro-4-fluorobenzyl)-5,6-dihydropyridin-2(1H)-one (10 g, 42 mmol) and KCN (8:0 g, 120 mmol) in DMF (400 mL) and water (100 mL) was warmed to 90° C. for 48 hours. The solvents were removed under reduced pressure and the residue was partitioned between EtOAc (250 mL) and water (100 mL). The organic phase was separated and the aqueous phase was extracted with more EtOAc (2×100 mL). The organic phases were combined and the solvent was removed under reduced pressure. The residue was purified by pressurized silica gel column chromatography eluting with 2:1:0.01 EtOAc:hexanes:MeOH. Fractions containing product were concentrated under reduced pressure to give the title compound as a solid. 1H NMR (400 MHz, CDCl3) δ 7.32 (dd, J=6.8, 2.0 Hz, 1H), 7.1-7.2 (m, 2H), 4.55 (AB quartet, J=17 Hz, 2H), 3.46 (ddd, J=13, 7.1, 6.5 Hz, 1H); 3.28 (ddd, J=13, 7.1, 6.5 Hz, 1H), 3.10 (m, 1H), 2.78 (ABX, J 17, 6.4 Hz, 2H), 2.2-2.2 (m, 2H); HPLC RT=2.36 min (Method A); ES MS M+1=267.

Workup

  1. customThe solvents were removed under reduced pressure
  2. customthe residue was partitioned between EtOAc (250 mL) and water (100 mL)
  3. customThe organic phase was separated
  4. extractionthe aqueous phase was extracted with more EtOAc (2×100 mL)
  5. customthe solvent was removed under reduced pressure
  6. customThe residue was purified by pressurized silica gel column chromatography
  7. washeluting with 2:1:0.01 EtOAc
  8. additionFractions containing product
  9. concentrationwere concentrated under reduced pressure

Sources & evidence

ORD record
ord-e9ada297b3c64718bedac873c018e943
Source dataset
uspto-grants-2009_11
Patent number
US07619086B2

Reaction notes

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