반응 #8651

반응 방정식

potassium carbonate

2,4-difluorophenylboronic acid

1-chloroisoquinoline

water

→

1-(2,4-difluoro-phenyl)-isoquinoline

용매

dimethoxyethane

반응 조건

후처리

1. 1
   온도at reflux for 20 h under N2
2. 2
   기타the organic and aqueous layers were separated
3. 3
   추출The aqueous layer was extracted with 3×150 mL of diethyl ether
4. 4
   건조the combined organic fractions were dried with sodium sulfate
5. 5
   여과filtered
6. 6
   기타the filtrate was evaporated to dryness
7. 7
   기타The crude material was chromatographed on a silica gel column
8. 8
   세척first by eluting the catalyst byproduct with 4:1 hexanes/CH2Cl2
9. 9
   세척finally the product was eluted with CH2Cl2/MeOH (9.5:0.5, product Rf=0.7)
10. 10
    기타The pure product fractions were collected
11. 11
    기타dried in vacuo
12. 12
    기타to afford
13. 13
    기타17.7 g (92% isolated yield) of a light yellow solid, >95% pure NMR spectroscopy

실험 절차

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).

출처