1,4-Dioxane → HCID 86695924、化合物

HRID 870931ノート

反応式

HRID 870931 の反応式
Cl[C:2]1[C:7]([C:8]([O-:10])=[O:9])=[CH:6][N:5]=[CH:4][C:3]=1[F:11].[Cl:12][C:13]1[CH:18]=[CH:17][C:16](B(O)O)=[C:15]([F:22])[CH:14]=1.P([O-])([O-])([O-])=O.[K+].[K+].[K+].O1CCOC[CH2:32]1>O.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2]>[Cl:12][C:13]1[CH:18]=[CH:17][C:16]([C:2]2[C:7]([C:8]([O:10][CH3:32])=[O:9])=[CH:6][N:5]=[CH:4][C:3]=2[F:11])=[C:15]([F:22])[CH:14]=1

参加物

7

反応物 4

HCID 312751,4-DioxaneHCID 62657Potassium Phosphate, TribasicHCID 4193595(4-Chloro-2-fluorophenyl)boronic acidHCID 86335698HCID 86335698、化合物

生成物 1

HCID 86695924HCID 86695924、化合物収率 50%

試薬・触媒・溶媒 2

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)触媒HCID 962Water溶媒

反応条件

温度
80 °C

実験手順

To a solution of 4-chloro-5-fluoronicotinate (1.2 g, 6.33 mmol) in 1,4-dioxane (12 mL) and water (0.5 mL) was added (4-chloro-2-fluorophenyl)boronic acid (1.214 g, 6.96 mmol) and potassium phosphate, dibasic (2.205 g, 12.66 mmol). To this mixture, PdCl2(dppf) (0.371 g, 0.506 mmol) was added and the solution purged with N2 for 10 min then heated to 80° C. for 12 h. The mixture was cooled to room temperature and water (25 mL) was added. The solution was extracted with ethyl acetate (3×25 mL). The combined organic layers were washed with brine (25 mL) and concentrated under reduced pressure to afford the residue which was purified by silica gel column using a gradient of ethyl acetate in hexanes to afford methyl 4-(4-chloro-2-fluorophenyl)-5-fluoronicotinate (900 mg, 3.17 mmol, 50% yield) as a yellow solid. LCMS (ESI) m/e 284.0 [(M+H)+, calcd for C13H9ClF2NO2 284.0]; LC/MS retention time (Method F): tR=1.01 min.

後処理

  1. customthe solution purged with N2 for 10 min
  2. temperatureThe mixture was cooled to room temperature
  3. additionwater (25 mL) was added
  4. extractionThe solution was extracted with ethyl acetate (3×25 mL)
  5. washThe combined organic layers were washed with brine (25 mL)
  6. concentrationconcentrated under reduced pressure
  7. customto afford the residue which
  8. customwas purified by silica gel column

出典と根拠

ORDレコード
ord-8e74e5d14c3a456d99b6dd438aafd92c
出典データセット
uspto-grants-2015_03
特許番号
US08969564B2

反応ノート

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