反应详情

温度

80 °C

DCE (0.146 mL, 1.69 mmol) was added to a vigorously stirred suspension of zinc dust (0.901 g, 13.8 mmol) in THF (3.5 mL) under nitrogen. The resulting suspension was heated at 80° C. for 10 minutes then cooled to room temperature. Trimethylsilyl chloride (0.202 mL, 1.59 mmol) in THF (1.75 mL) was added and the mixture was stirred at room temperature for 4 minutes. A solution of tert-butyl 3-iodoazetidine-1-carboxylate (3.00 g, 10.6 mmol) in THF (3.5 mL) was added dropwise over 15 minutes and the resulting mixture stirred at room temperature for 2 hours. Pd2(dba)3 (0.155 g, 0.170 mmol) and tri-2-furylphosphine (0.143 g, 0.615 mmol) were added followed by 1-iodo-4-nitrobenzene (2.90 g, 11.7 mmol) in THF (18 mL). The resulting mixture was then heated at 55° C. for 3 hours then quenched with an aqueous saturated sodium chloride solution (15 mL). After filtration through a pad of Celite, the layers were separated and the aqueous phase extracted with DCM (2×15 mL). The combined organic fractions were dried (MgSO4), filtered and evaporated in vacuo. The residue was purified using silica gel column chromatography (CombiFlash Rf, 40 g SiO2 cartridge, 10-40% EtOAc in cyclohexane) to give the title compound A76 as an orange oil (2.14 g, 72%); 1H NMR (300 MHz, CDCl3) δ 8.24 (dd, J=6.8, 1.9 Hz, 2H), 7.51 (d, J=8.6 Hz, 2H), 4.41 (t, J=8.7 Hz, 2H), 3.98 (dd, J=8.5, 5.7 Hz, 2H), 3.89-3.81 (s, 1H), 1.49 (s, 9H).

1. temperaturethen cooled to room temperature
2. stirringthe resulting mixture stirred at room temperature for 2 hours
3. temperatureThe resulting mixture was then heated at 55° C. for 3 hours
4. customthen quenched with an aqueous saturated sodium chloride solution (15 mL)
5. filtrationAfter filtration through a pad of Celite
6. customthe layers were separated
7. extractionthe aqueous phase extracted with DCM (2×15 mL)
8. dry with materialThe combined organic fractions were dried (MgSO4)
9. filtrationfiltered
10. customevaporated in vacuo
11. customThe residue was purified