反应详情

温度

100 °C

To a mixture under N2 of 5-fluoro-8-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-3,4-dihydro-1H-isoquinoline-2-carboxylic acid benzyl ester (82 mg, 0.20 mmol, 1.00 eq.), (±)-2-(3-bromo-4-methoxy-phenyl)-propionic acid ethyl ester (63 mg, 0.20 mmol, 1.00 eq.) and sodium carbonate (85 mg, 0.80 mmol, 4.00 eq.) in toluene/MeOH/water 20:4:1 (4 mL), tetrakis(triphenylphosphine) palladium (0) (12 mg, 0.01 mmol, 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 (10 mL) and water (10 mL). The layers were separated. The org. phase was washed with sat. aq. NaCl soln. (1×5 mL), dried over MgSO4 and filtered through Celite. The filtrate was concentrated in vacuo. To a solution of the previous residue in DMF (0.9 mL), 1M aq. NaOH soln. (1.3 mL) was added. The mixture was stirred at 50° C. for 18 hours. The reaction mixture was concentrated in vacuo. The residue was redissolved in THF (2 mL) and water (2 mL). Lithiumhydroxide monohydrate (23 mg, 0.54 mmol, 2.71 eq.) was added and the mixture was stirred at 50° C. for 18 hours. Formic acid was added (0.2 mL). The solution was diluted with DCM. The layers were separated and the aq. phase was extracted with DCM (2×). The comb. org. layers were dried over MgSO4, filtered and concentrated in vacuo.

1. temperatureto cool to r.t.
2. concentrationconcentrated in vacuo
3. customThe residue was partitioned between AcOEt (10 mL) and water (10 mL)
4. customThe layers were separated
5. washphase was washed with sat. aq. NaCl soln
6. dry with material(1×5 mL), dried over MgSO4
7. filtrationfiltered through Celite
8. concentrationThe filtrate was concentrated in vacuo
9. addition(1.3 mL) was added
10. stirringThe mixture was stirred at 50° C. for 18 hours
11. concentrationThe reaction mixture was concentrated in vacuo
12. dissolutionThe residue was redissolved in THF (2 mL)
13. stirringthe mixture was stirred at 50° C. for 18 hours
14. customThe layers were separated
15. extractionthe aq. phase was extracted with DCM (2×)
16. dry with materiallayers were dried over MgSO4
17. filtrationfiltered
18. concentrationconcentrated in vacuo