Water → 1-(2,4-Difluorophenyl)isoquinoline

HRID 8555

Reaktionsgleichung

Reaktionsgleichung von HRID 8555
[F:1][C:2]1[CH:7]=[C:6]([F:8])[CH:5]=[CH:4][C:3]=1B(O)O.Cl[C:13]1[C:22]2[C:17](=[CH:18][CH:19]=[CH:20][CH:21]=2)[CH:16]=[CH:15][N:14]=1.C(=O)([O-])[O-].[K+].[K+].O>C(COC)OC>[F:1][C:2]1[CH:7]=[C:6]([F:8])[CH:5]=[CH:4][C:3]=1[C:13]1[C:22]2[C:17](=[CH:18][CH:19]=[CH:20][CH:21]=2)[CH:16]=[CH:15][N:14]=1

Komponenten

6

Edukt 4

HCID 962WaterHCID 11430Potassium CarbonateHCID 140539Isoquinoline, 1-chloro-HCID 27343342,4-Difluorophenylboronic acid

Produkt 1

HCID 219094191-(2,4-Difluorophenyl)isoquinoline

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 80711,2-DimethoxyethaneLösungsmittel

Versuchsvorschrift

2,4-difluorophenylboronic acid (Aldrich Chemical Co., 13.8 g, 87.4 mmol), 1-chloroisoquinoline (Adrich Chemical Co., 13 g, 79.4 mmol), tetrakistriphenylphosphine palladium(0) (Aldrich, 3.00 g, 2.59 mmol), potassium carbonate (EM Science, 24.2 g, 175 mmol), water (300 mL), and dimethoxyethane (Aldrich, 300 mL) were allowed to stir at reflux for 20 h under N2, after which time the mixture was cooled to room temperature and the organic and aqueous layers were separated. The aqueous layer was extracted with 3×150 mL of diethyl ether, and the combined organic fractions were dried with sodium sulfate, filtered, and the filtrate was evaporated to dryness. The crude material was chromatographed on a silica gel column, first by eluting the catalyst byproduct with 4:1 hexanes/CH2Cl2, and finally the product was eluted with CH2Cl2/MeOH (9.5:0.5, product Rf=0.7). The pure product fractions were collected and dried in vacuo, to afford 17.7 g (92% isolated yield) of a light yellow solid, >95% pure NMR spectroscopy. 1H NMR (CDCl3, 296 K, 300 MHz): δ 8.61 (1H, d, J=5.7 Hz), 7.89 (1H, d, J=8.2 Hz), 7.67–7.85 (3H, m), 7.52–7.63 (2H, m), 6.95–7.12 (2H, m) ppm. 19F NMR (CDCl3, 296K, 282 MHz) δ −109.01 (1F, brs), −109.87 (1F, d, JF-F=8.5 Hz).

Aufarbeitung

  1. temperatureat reflux for 20 h under N2
  2. customthe organic and aqueous layers were separated
  3. extractionThe aqueous layer was extracted with 3×150 mL of diethyl ether
  4. dry with materialthe combined organic fractions were dried with sodium sulfate
  5. filtrationfiltered
  6. customthe filtrate was evaporated to dryness
  7. customThe crude material was chromatographed on a silica gel column
  8. washfirst by eluting the catalyst byproduct with 4:1 hexanes/CH2Cl2
  9. washfinally the product was eluted with CH2Cl2/MeOH (9.5:0.5, product Rf=0.7)
  10. customThe pure product fractions were collected
  11. customdried in vacuo
  12. customto afford
  13. custom17.7 g (92% isolated yield) of a light yellow solid, >95% pure NMR spectroscopy

Quellen und Nachweise

ORD-Eintrag
ord-08a08e084a414c518c9108c5bc2b198d
Quelldatensatz
uspto-grants-2006_08
Patentnummer
US07090929B2

Verknüpfte Notizen

Wird geladen…