Potassium Phosphate, Tribasic → HCID 86695924、化合物

HRID 1398451ノート

反応式

HRID 1398451 の反応式
Cl[C:2]1[C:7]([C:8]([O:10][CH3:11])=[O:9])=[CH:6][N:5]=[CH:4][C:3]=1[F:12].[Cl:13][C:14]1[CH:19]=[CH:18][C:17](B(O)O)=[C:16]([F:23])[CH:15]=1.P([O-])([O-])([O-])=O.[K+].[K+].[K+]>O1CCOCC1.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:13][C:14]1[CH:19]=[CH:18][C:17]([C:2]2[C:7]([C:8]([O:10][CH3:11])=[O:9])=[CH:6][N:5]=[CH:4][C:3]=2[F:12])=[C:16]([F:23])[CH:15]=1

参加物

7

反応物 3

HCID 62657Potassium Phosphate, TribasicHCID 4193595(4-Chloro-2-fluorophenyl)boronic acidHCID 86695923Methyl 4-chloro-5-fluoropyridine-3-carboxylate

生成物 1

HCID 86695924HCID 86695924、化合物収率 50.1%

試薬・触媒・溶媒 3

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)触媒HCID 962Water溶媒HCID 312751,4-Dioxane溶媒

反応条件

温度
80 °C

実験手順

To a solution of methyl 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). The mixture was then purged with nitrogen gas for 5 min. Potassium phosphate, dibasic (2.205 g, 12.66 mmol) and PdCl2(dppf) (0.371 g, 0.506 mmol) were added and again the mixture was purged with N2 for 5 min. The reaction mixture was heated to 80° C. for 12 h. After cooling, water was added to and the mixture was extracted with ethyl acetate (3×25 mL). The combined organic layers were washed with brine, dried over sodium sulfate and concentrated under reduced pressure. The residue was purified by silica gel chromatography using hexane and ethyl acetate to afford methyl 4-(4-chloro-2-fluorophenyl)-5-fluoronicotinate (900 mg, 3.17 mmol, 50% yield) as a yellow solid. LC/MS (ESI) m/e 284.0 [(M+H)+, calcd for C13H9ClF2NO2 284.02]; LC/MS retention time (method D): tR=1.01 min.

後処理

  1. customThe mixture was then purged with nitrogen gas for 5 min
  2. customagain the mixture was purged with N2 for 5 min
  3. temperatureAfter cooling
  4. additionwater was added to and the mixture
  5. extractionwas extracted with ethyl acetate (3×25 mL)
  6. washThe combined organic layers were washed with brine
  7. dry with materialdried over sodium sulfate
  8. concentrationconcentrated under reduced pressure
  9. customThe residue was purified by silica gel chromatography

出典と根拠

ORDレコード
ord-48aceb7ed8454f6fb9fec8decdc7b651
出典データセット
uspto-grants-2014_12
特許番号
US08901305B2

反応ノート

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