反应详情

温度

100 °C

To a mixture under N2 of (±)-2-bromo-4-(5-chloro-2-ethoxycarbonylmethoxy-phenyl)-6,7-dihydro-4H-thiazolo[5,4-c]pyridine-5-carboxylic acid benzyl ester (63 mg, 0.12 mmol, 1.00 eq.), phenylboronic acid (15 mg, 0.12 mmol, 1.00 eq.) and sodium carbonate (50 mg, 0.47 mmol, 4.00 eq.) in toluene/MeOH/Water 20:4:1 (4 mL), tetrakis(triphenylphosphine) palladium (0) (6.8 mg, 6 μmol, 0.05 eq.) was added and the mixture was stirred at 100° C. for 18 hours. The mixture was allowed to cool to r.t. and concentrated in vacuo. The residue was partitioned between AcOEt (25 mL) and water (25 mL). The layers were separated. The org. phase was washed with sat. aq. NaCl soln. (1×12 mL), dried over MgSO4 and filtered through Celite. The filtrate was concentrated in vacuo. The residue was dissolved in DMF (0.5 mL), 1M aq. NaOH soln. (0.5 mL) was added. The resulting solution was stirred at r.t. for 18 hours. The solution was neutralized with formic acid (1 mL), filtered, and then purified by prep. HPLC (column: Atlantis, 30×75 mm, 10 um, UV/MS, acidic conditions) and concentrated in vacuo to give the desired acid as a white solid.

1. temperatureto cool to r.t.
2. concentrationconcentrated in vacuo
3. customThe residue was partitioned between AcOEt (25 mL) and water (25 mL)
4. customThe layers were separated
5. washphase was washed with sat. aq. NaCl soln
6. dry with material(1×12 mL), dried over MgSO4
7. filtrationfiltered through Celite
8. concentrationThe filtrate was concentrated in vacuo
9. dissolutionThe residue was dissolved in DMF (0.5 mL)
10. addition(0.5 mL) was added
11. stirringThe resulting solution was stirred at r.t. for 18 hours
12. filtrationfiltered
13. custompurified by prep
14. concentrationHPLC (column: Atlantis, 30×75 mm, 10 um, UV/MS, acidic conditions) and concentrated in vacuo