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

HRID 40346

반응식

HRID 40346 반응식
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

참가 물질

9

반응물 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

생성물 1

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

시약·촉매·용매 4

HCID 167845palladium(II) acetate촉매HCID 962Water용매HCID 8857Ethyl Acetate용매2회HCID 312751,4-Dioxane용매

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온도
100 °C

실험 절차

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.

후처리

  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

출처 및 근거

ORD 기록
ord-d9fac620b91544978d069c4c72220021
출처 데이터셋
uspto-grants-2013_09
특허 번호
US08524900B2

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