反应详情

温度

90 °C

A solution of 6-(4-bromo-2,6-dichloro-benzyl)-4-isopropyl-pyridazin-3-one (51) (194 mg, 0.516 mmol) in acetonitrile (10 mL) and methanol (2 mL) at room temperature was treated with palladium(II) acetate (23.7 mg, 0.106 mmol), 1,3-bis(diphenylphosphino)propane (45.7 mg, 0.111 mmol) and triethylamine (360 μL, 2.58 mmol). The sealed tube was then pressurized to 45 psi with carbon monoxide and heated to 90° C. for 1 h. The reaction was cooled to room temperature, the pressure was released and a TLC was taken of the reaction mixture which indicated that starting material was still present. Additional palladium(II) acetate (10 mg) and 1,3-bis(diphenylphosphino)propane (20 mg) were added to the reaction mixture. The sealed tube was then pressurized to 45 psi with carbon monoxide and heated to 90° C. for another 1.5 h. The reaction was cooled to room temperature, the pressure was released and the reaction mixture was diluted with ethyl acetate (100 mL) and was washed with 1:1 solution of water (30 mL) and a saturated aqueous sodium chloride solution (30 mL). The organic layer was separated, dried with magnesium sulfate, filtered and concentrated. The resulting residue was purified by flash chromatography using silica gel eluted with a gradient of 4:1 to 1:1 ethyl acetate:hexanes. The desired fractions were collected and concentrated under vacuum to afford a solid which was dried under high vacuum to afford 3,5-dichloro-4-(5-isopropyl-6-oxo-1,6-dihydro-pyridazin-3-ylmethyl)-benzoic acid methyl ester (52) (183 mg, 90%) as an off-white solid; LRMS-ES(+) for C16H16Cl2N2O3 (M+H) m/z=355. MW=355.2235, Exact Mass=354.0538

1. temperatureThe reaction was cooled to room temperature
2. temperatureheated to 90° C. for another 1.5 h
3. temperatureThe reaction was cooled to room temperature
4. washwas washed with 1:1 solution of water (30 mL)
5. customThe organic layer was separated
6. dry with materialdried with magnesium sulfate
7. filtrationfiltered
8. concentrationconcentrated
9. customThe resulting residue was purified by flash chromatography
10. washeluted with a gradient of 4:1 to 1:1 ethyl acetate
11. customThe desired fractions were collected
12. concentrationconcentrated under vacuum
13. customto afford a solid which
14. customwas dried under high vacuum