反应详情

温度

115 °C

To a solution of potassium phosphate, tribasic (0.564 g, 2.66 mmol), potassium phenyltrifluoroborate (0.245 g, 1.330 mmol), and 8-chloro-2-methyl-3-oxo-3,4-dihydro-2H-benzo[b][1,4]oxazine-6-carbaldehyde 15 (0.2 g, 0.886 mmol) in toluene (Ratio: 4.00, 16 mL) and water (Ratio: 1.000, 4.0 mL) was added PdOAc2 (0.015 g, 0.066 mmol) and dicyclohexyl(2′,6′-diisopropoxybiphenyl-2-yl)phosphine (0.062 g, 0.133 mmol) at 23° C. The reaction was stirred at 115° C. for 42 hr. The reaction mixture was poured into water (2 mL) and extracted with Et2O (3×5 mL). The organic layer was dried over Na2SO4, filtered, and the organic phase stripped to dryness via rotary evaporation. The resulting crude material was purified via medium pressure chromatography using a gradient eluant of CH2Cl2/MeOH. The appropriate fractions were combined and concentrated via rotary evaporation. The impure material was reconstituted in DMSO (1.0 mL) and purified via preparative mass trigger LCMS using a gradient eluant of 45-70% ACN:0.05% TFA (aq). The early fractions were combined and the solvent was removed via rotary evaporation. The purified product was dried in vacuo to provide the title compound as an off-white solid (0.0459 g, 0.172 mmol, 19.37% yield). 1H NMR (400 MHz, DMSO-d6) δ ppm 1.44 (d, J=6.82 Hz, 3H) 4.85-4.92 (m, 1H) 7.38-7.43 (m, 2H) 7.46-7.51 (m, 2H) 7.57-7.62 (m, 2H) 7.64 (d, J=2.02 Hz, 1H) 9.91 (s, 1H) 11.04 (s, 1H). ESI-MS: m/z 268.1 (M+H)+.

1. customat 23° C
2. extractionextracted with Et2O (3×5 mL)
3. dry with materialThe organic layer was dried over Na2SO4
4. filtrationfiltered
5. customthe organic phase stripped to dryness via rotary evaporation
6. customThe resulting crude material was purified via medium pressure chromatography
7. concentrationconcentrated via rotary evaporation
8. custompurified via preparative mass trigger LCMS
9. customthe solvent was removed via rotary evaporation
10. customThe purified product was dried in vacuo