反应详情

温度

115 °C

Ethyl 2-(7-((3,4-difluorobenzyl)oxy)-1,5-naphthyridin-3-yl)acetate. 3-Bromo-7-((3,4-difluorobenzyl)oxy)-1,5-naphthyridine (3.20 g, 9.11 mmol), Pd2(dba)3 (41.72 mg, 0.05 mmol), tri-tert-butylphosphonium tetrafluoroborate (290.84 mg, 1 mmol), potassium phosphate (5.42 g, 25.52 mmol), 1,4,7,10,13,16-hexaoxacyclooctadecane (1.2 g, 4.56 mmol), and diethyl malonate (9.17 mL, 60.15 mmol) were added to a microwave vial, which was capped and purged with nitrogen for several minutes then heated to 115° C. for 19 h. The reaction was cooled to ambient temperature then water and EtOAc were added. The layers were separated and the aqueous solution was extracted with EtOAc and DCM. The combined organic layers were washed with brine then dried (Na2SO4). The solvent was removed under reduced pressure. Purification (FCC, SiO2, 0-70%, EtOAc/hexanes) afforded the title compound as a pure beige solid (1.76 g, 53.8%). 1H NMR (400 MHz, CDCl3) δ 8.84 (dd, J=18.1, 2.5 Hz, 2H), 8.27 (d, J=1.4 Hz, 1H), 7.68 (d, J=2.6 Hz, 1H), 7.47-7.30 (m, 1H), 7.26-7.17 (m, 2H), 5.20 (s, 2H), 4.22 (q, J=7.2 Hz, 2H), 3.86 (s, 2H), 1.30 (t, J=7.2 Hz, 3H). [M+H]=359.2.

1. customwas capped
2. custompurged with nitrogen for several minutes
3. temperatureThe reaction was cooled to ambient temperature
4. additionwater and EtOAc were added
5. customThe layers were separated
6. extractionthe aqueous solution was extracted with EtOAc and DCM
7. washThe combined organic layers were washed with brine
8. dry with materialthen dried (Na2SO4)
9. customThe solvent was removed under reduced pressure
10. customPurification (FCC, SiO2, 0-70%, EtOAc/hexanes)