Cesium fluoride → Methyl 4-amino-6-(4-chloro-3-fluorophenyl)-5-fluoropicolinate

HRID 244319

反応式

HRID 244319 の反応式
[NH2:1][C:2]1[C:7]([F:8])=[C:6](Cl)[N:5]=[C:4]([C:10]([O:12][CH3:13])=[O:11])[CH:3]=1.[Cl:14][C:15]1[CH:20]=[CH:19][C:18](B(O)O)=[CH:17][C:16]=1[F:24].[F-].[Cs+]>Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1>[NH2:1][C:2]1[C:7]([F:8])=[C:6]([C:18]2[CH:19]=[CH:20][C:15]([Cl:14])=[C:16]([F:24])[CH:17]=2)[N:5]=[C:4]([C:10]([O:12][CH3:13])=[O:11])[CH:3]=1

参加物

5

反応物 3

HCID 25953Cesium fluorideHCID 27786564-Chloro-3-fluorophenylboronic AcidHCID 86668302Methyl 4-amino-6-chloro-5-fluoropicolinate

生成物 1

HCID 70498547Methyl 4-amino-6-(4-chloro-3-fluorophenyl)-5-fluoropicolinate収率 71%

試薬・触媒・溶媒 1

HCID 178418476HCID 178418476、化合物触媒

反応条件

温度
85 °C

実験手順

Methyl 4-amino-6-chloro-5-fluoropicolinate (3.0 g, 14.66 mmol), (4-chloro-3-fluorophenyl)boronic acid (3.07 g, 17.60 mmol), bis(triphenylphosphine)palladium(II) dichloride (1.029 g, 1.466 mmol), and cesium fluoride (4.45 g, 29.3 mmol) were comined in a flask that was sealed and purged with nitrogen. Dioxane (50 ml) and Water (10.00 ml) were added and the reaction mixture was heated at 85° C. for 18 hrs. The reaction mixture was diluted with ethyl acetate and water. The organic phase was washed with saturated sodium chlride, dried over magnesium sulfate, filtered, and concentrated onto silica. The product was purified by flash chromatography (SiO2, 0-40% EtOAc:Hex gradient) to provide the title compound (3.11 g, 10.41 mmol, 71.0% yield) as a white solid: 1H NMR (400 MHz, DMSO-d6) d 3.85 (s, 3H), 6.72 (s, 2H), 7.49 (d, J=6.3 Hz, 1H), 7.68-7.80 (m, 2H), 7.84 (dd, J=10.8, 1.3 Hz, 1H); 19F NMR (376 MHz, DMSO-d6) d −144.47, −116.07; ESIMS m/z 299 ([M+H]+).

後処理

  1. customthat was sealed
  2. custompurged with nitrogen
  3. additionDioxane (50 ml) and Water (10.00 ml) were added
  4. additionThe reaction mixture was diluted with ethyl acetate and water
  5. washThe organic phase was washed with saturated sodium chlride
  6. dry with materialdried over magnesium sulfate
  7. filtrationfiltered
  8. concentrationconcentrated onto silica
  9. customThe product was purified by flash chromatography (SiO2, 0-40% EtOAc:Hex gradient)

出典と根拠

ORDレコード
ord-27a9f8f056f84a8891d81a0b5c45f50b
出典データセット
uspto-grants-2014_02
特許番号
US08658568B2

関連ノート

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