Potassium Phosphate, Tribasic → 5-(3,5-Difluorophenyl)-2,3-difluoropyridine

HRID 40313

反応式

HRID 40313 の反応式
P([O-])([O-])([O-])=O.[K+].[K+].[K+].[F:9][C:10]1[CH:11]=[C:12](B(O)O)[CH:13]=[C:14]([F:16])[CH:15]=1.CC(C1C=C(C(C)C)C(C2C=CC=CC=2P(C2CCCCC2)C2CCCCC2)=C(C(C)C)C=1)C.Cl[C:55]1[CH:56]=[C:57]([F:62])[C:58]([F:61])=[N:59][CH:60]=1>O1CCOCC1.O.C([O-])(=O)C.[Pd+2].C([O-])(=O)C>[F:9][C:10]1[CH:11]=[C:12]([C:55]2[CH:56]=[C:57]([F:62])[C:58]([F:61])=[N:59][CH:60]=2)[CH:13]=[C:14]([F:16])[CH:15]=1

参加物

8

反応物 4

HCID 62657Potassium Phosphate, TribasicHCID 2734338(3,5-Difluorophenyl)boronic acidHCID 27832485-Chloro-2,3-difluoropyridineHCID 111557942-Dicyclohexylphosphino-2',4',6'-triisoprophylbiphenyl

生成物 1

HCID 675027115-(3,5-Difluorophenyl)-2,3-difluoropyridine

試薬・触媒・溶媒 3

HCID 167845palladium(II) acetate触媒HCID 962Water溶媒HCID 312751,4-Dioxane溶媒

反応条件

温度
100 °C

実験手順

A mixture of palladium (II) acetate (0.0375 g, 0.167 mmol), potassium phosphate (2.13 g, 10.0 mmol), 3,5-difluorophenylboronic acid (1.58 g, 10.0 mmol), X-Phos (0.159 g, 0.334 mmol) and 5-chloro-2,3-difluoropyridine (0.347 ml, 3.34 mmol) was diluted with 1,4-dioxane (0.1M, 33.4 mL) and water (0.3M, 11.0 mL) and was heated under nitrogen at 100° C. for 45 minutes. The reaction was concentrated in vacuo. The concentrated material was triturated with water, filtered and rinsed with MeCN. The crude solid was taken up in dichloromethane and filtered over a plug of Celite to eliminate residual palladium. The material was dissolved in minimal DCM, and purified via MPLC (eluting with 0-10% EtOAc in hexanes) to yield 5-(3,5-difluorophenyl)-2,3-difluoropyridine. The material was converted to the hydrazine in a method similar to that in the synthesis of (S)-6-(1-(8-fluoro-6-(3-methylisothiazol-5-yl)-[1,2,4]triazolo[4,3-α]pyridin-3-yl)ethyl)quinoline.

後処理

  1. concentrationThe reaction was concentrated in vacuo
  2. customThe concentrated material was triturated with water
  3. filtrationfiltered
  4. washrinsed with MeCN
  5. filtrationfiltered over a plug of Celite
  6. dissolutionThe material was dissolved in minimal DCM
  7. custompurified via MPLC (eluting with 0-10% EtOAc in hexanes)

出典と根拠

ORDレコード
ord-f8a17af4ee534c619b8a9a42877539c8
出典データセット
uspto-grants-2013_09
特許番号
US08524900B2

関連ノート

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