Реакция #2286315

Уравнение реакции

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

Выход 90.0%

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

Выход 90.0%

Растворители

acetonitrile

methanol

Условия реакции

Обработка

1. 1
   ТемператураThe reaction was cooled to room temperature
2. 2
   Температураheated to 90° C. for another 1.5 h
3. 3
   ТемператураThe reaction was cooled to room temperature
4. 4
   Промывкаwas washed with 1:1 solution of water (30 mL)
5. 5
   ДругоеThe organic layer was separated
6. 6
   Сушкаdried with magnesium sulfate
7. 7
   Фильтрацияfiltered
8. 8
   Концентрированиеconcentrated
9. 9
   ДругоеThe resulting residue was purified by flash chromatography
10. 10
    Промывкаeluted with a gradient of 4:1 to 1:1 ethyl acetate
11. 11
    ДругоеThe desired fractions were collected
12. 12
    Концентрированиеconcentrated under vacuum
13. 13
    Другоеto afford a solid which
14. 14
    Другоеwas dried under high vacuum

Методика

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

Источник