Potassium Phosphate, Tribasic → 2,3-difluoro-5-(1-methyl-1H-pyrazol-4-yl)pyridine

HRID 40346

反応式

HRID 40346 の反応式
Cl[C:2]1[CH:3]=[C:4]([F:9])[C:5]([F:8])=[N:6][CH:7]=1.[O-]P([O-])([O-])=O.[K+].[K+].[K+].[CH3:18][N:19]1[CH:23]=[C:22](B2OC(C)(C)C(C)(C)O2)[CH:21]=[N:20]1.CC(C1C=C(C(C)C)C(C2C=CC=CC=2P(C2CCCCC2)C2CCCCC2)=C(C(C)C)C=1)C>C([O-])(=O)C.[Pd+2].C([O-])(=O)C.CCOC(C)=O.O.O1CCOCC1>[F:8][C:5]1[C:4]([F:9])=[CH:3][C:2]([C:22]2[CH:21]=[N:20][N:19]([CH3:18])[CH:23]=2)=[CH:7][N:6]=1

参加物

9

反応物 4

HCID 62657Potassium Phosphate, TribasicHCID 27739871-Methyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazoleHCID 27832485-Chloro-2,3-difluoropyridineHCID 111557942-Dicyclohexylphosphino-2',4',6'-triisoprophylbiphenyl

生成物 1

HCID 576913652,3-difluoro-5-(1-methyl-1H-pyrazol-4-yl)pyridine収率 88.5%

試薬・触媒・溶媒 4

HCID 167845palladium(II) acetate触媒HCID 962Water溶媒HCID 8857Ethyl Acetate溶媒2 回HCID 312751,4-Dioxane溶媒

反応条件

温度
100 °C

実験手順

A sealable flask was charged with 5-chloro-2,3-difluoropyridine (1.541 g, 10.3 mmol), palladium(ii) acetate (0.116 g, 0.515 mmol), potassium phosphate tribasic (6.56 g, 30.9 mmol), 1-methyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole (2.57 g, 12.4 mmol), and X-Phos (0.491 g, 1.03 mmol). The flask was sealed with a septum cap, then dioxane (20 mL) and H2O (2 mL) were added. The resulting mixture was sparged with N2 for 10 min, and then heated at 100° C. for 2 h. The solution was cooled to rt and then concentrated and purified by flash chromatography using eluent 99:1 Hexanes:EtOAc to 60:40 Hexanes:EtOAc gradient to afford 2,3-difluoro-5-(1-methyl-1H-pyrazol-4-yl)pyridine (1.78 g, 88.5% yield) as a colorless film. LRMS (ESI) m/z calcd for C9H7F2N3 (M+H) 197.1. found 197.4.

後処理

  1. customThe flask was sealed with a septum
  2. customcap
  3. customThe resulting mixture was sparged with N2 for 10 min
  4. temperatureThe solution was cooled to rt
  5. concentrationconcentrated
  6. custompurified by flash chromatography

出典と根拠

ORDレコード
ord-d9fac620b91544978d069c4c72220021
出典データセット
uspto-grants-2013_09
特許番号
US08524900B2

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