反应 #2286315

反应方程式

carbon monoxide

ethyl acetate

carbon monoxide

6-(4-bromo-2,6-dichloro-benzyl)-4-isopropyl-pyridazin-3-one

1,3-bis(diphenylphosphino)propane

triethylamine

→

3,5-dichloro-4-(5-isopropyl-6-oxo-1,6-dihydro-pyridazin-3-ylmethyl)-benzoic acid methyl ester

收率 90.0%

3,5-Dichloro-4-(5-isopropyl-6-oxo-1,6-dihydro-pyridazin-3-ylmethyl)-benzoic acid methyl ester

收率 90.0%

溶剂

acetonitrile

methanol

反应条件

后处理

1. 1
   温度The reaction was cooled to room temperature
2. 2
   温度heated to 90° C. for another 1.5 h
3. 3
   温度The reaction was cooled to room temperature
4. 4
   洗涤was washed with 1:1 solution of water (30 mL)
5. 5
   其他The organic layer was separated
6. 6
   干燥dried with magnesium sulfate
7. 7
   过滤filtered
8. 8
   浓缩concentrated
9. 9
   其他The resulting residue was purified by flash chromatography
10. 10
    洗涤eluted with a gradient of 4:1 to 1:1 ethyl acetate
11. 11
    其他The desired fractions were collected
12. 12
    浓缩concentrated under vacuum
13. 13
    其他to afford a solid which
14. 14
    其他was dried under high vacuum

实验过程

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

来源