反应详情

温度

120 °C

To a mixture of 3-chloro-7-methoxy-4-methylisoquinoline (Intermediate 15) (470 mg, 2.27 mmol), 4-carboxyphenylboronic acid (451 mg, 2.72 mmol) and K2CO3 (627 mg, 4.54 mmol) in DEGME/H2O (7 mL/1 mL) was added Pd(dppf)Cl2 (40.8 mg, 0.050 mmol) under N2 atmosphere. Then the mixture was heated to 120° C. for 16 hours. H2O (30 mL) was added, and the resulting mixture was extracted with EtOAc (15 mL×2). The aqueous layer was neutralized with 1N aqueous HCl to pH=7, extracted with EtOAc (20 mL×3). The combined organic layers were washed with H2O (20 mL) and brine (20 mL), dried over anhydrous Na2SO4, filtered and concentrated. Purification by silica gel column (PE/EtOAc=20/1 to 1/1, then EtOAc) gave 4-(7-methoxy-4-methylisoquinolin-3-yl)benzoic acid (85.0 mg, yield 13%).

1. extractionthe resulting mixture was extracted with EtOAc (15 mL×2)
2. extractionextracted with EtOAc (20 mL×3)
3. washThe combined organic layers were washed with H2O (20 mL) and brine (20 mL)
4. dry with materialdried over anhydrous Na2SO4
5. filtrationfiltered
6. concentrationconcentrated
7. customPurification by silica gel column (PE/EtOAc=20/1 to 1/1