反应详情

Methyl 4-bromo-3-methylbenzoate (Intermediate 17, step 1) (3 g; 13.10 mmol; 1 eq.), 2-biphenylboronic acid (2 852.77 mg; 14.41 mmol; 1.10 eq.), potassium carbonate (9.05 g; 65.48 mmol; 5 eq.), tetrakis(triphenylphosphine)palladium(0) (1.51 g; 1.31 mmol; 0.10 eq.) were taken in Toluene (15 mL) and water (15 mL) under N2 atmosphere. The reaction mixture was purged with vacuum, then degassed with N2 and then refluxed for 3 hours. The reaction mixture was cooled to RT, filtered over a pad of celite and washed with toluene (200 mL). The filtrate was concentrated to afford brown oil, which was taken in EtOAc (200 mL). The organic layer was washed with a saturated aqueous solution of NaHCO3 solution (70 mL), water (70 mL) and brine (70 mL), dried over MgSO4 and concentrated affording methyl 2-methyl-1,1′:2′,1″-terphenyl-4-carboxylate as a brown oil (3.9 g, 98%, HPLC (Method A) Rt 5.51 min), which was used further without purification. A solution of methyl 2-methyl-1,1′:2′,1″-terphenyl-4-carboxylate (3.50 g; 11.58 mmol; 1 eq.) in EtOH (105 mL) at rt was treated with sodium hydroxide (6.95 mL; 5 M; 34.73 mmol; 3 eq.). The reaction mixture was stirred at 60° C. for 1 hour. The reaction mixture was concentrated giving a brown solid. It was taken up in water (400 mL) and the aqueous phase was washed twice with EtOAc. The aqueous phase was acidified with HCl cc (2 mL) to pH 2, then it was concentrated until precipitation (volume divided /5). The suspension was filtered affording the title compound as an orange solid (2.41 g, 72%). 1H NMR (DMSO-d6, 300 MHz) δ 12.71 (br s, 1H), 7.54-6.91 (m, 12H), 1.76 (s, 3H). LC/MS (Method A): 286.9 (M−H)−. HPLC (Method A) Rt 4.85 min (Purity: 97.1%).

1. customThe reaction mixture was purged with vacuum
2. customdegassed with N2
3. temperaturerefluxed for 3 hours
4. filtrationfiltered over a pad of celite
5. washwashed with toluene (200 mL)
6. concentrationThe filtrate was concentrated
7. customto afford brown oil, which
8. washThe organic layer was washed with a saturated aqueous solution of NaHCO3 solution (70 mL), water (70 mL) and brine (70 mL)
9. dry with materialdried over MgSO4
10. concentrationconcentrated