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

HRID 1436888ノート

反応式

HRID 1436888 の反応式
[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]

参加物

5

反応物 2

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

生成物 1

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

試薬・触媒・溶媒 2

HCID 962Water溶媒HCID 6228Dimethylformamide溶媒

反応条件

温度
90 °C

実験手順

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.

後処理

  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

出典と根拠

ORDレコード
ord-e9ada297b3c64718bedac873c018e943
出典データセット
uspto-grants-2009_11
特許番号
US07619086B2

反応ノート

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