Sodium hydride → 3-cyclopentyl-2-(4,5-dichloro-6-oxo-6H-pyridazin-1-yl)-propionic acid methyl ester
Reaction equation
[Cl:1][C:2]1[C:3](=[O:9])[NH:4][N:5]=[CH:6][C:7]=1[Cl:8].[H-].[Na+].[CH3:12][O:13][C:14](=[O:23])[CH:15](Br)[CH2:16][CH:17]1[CH2:21][CH2:20][CH2:19][CH2:18]1>O1CCCC1>[CH3:12][O:13][C:14](=[O:23])[CH:15]([N:4]1[C:3](=[O:9])[C:2]([Cl:1])=[C:7]([Cl:8])[CH:6]=[N:5]1)[CH2:16][CH:17]1[CH2:18][CH2:19][CH2:20][CH2:21]1Participants
Reactant 3
Product 1
Reagents, catalysts & solvents 1
Conditions
- Temperature
- 0 °C
Procedure
A solution of 4,5-dichloropyridazin-3(2H)-one (25.5 g, 154 mmol) in tetrahydrofuran was treated with 60% sodium hydride (7.42 g, 185.5 mmol) at 0° C. The reaction was stirred at 0° C. for 10 min, and then stirred at 25° C. for 1 h. At this time, the reaction was treated with 2-bromo-3-cyclopentyl-propionic acid methyl ester (Intermediate 10, 54.5 g, 185.5 mmol), and was stirred for 2 d at 50° C. The reaction solution was partitioned between water and ethyl acetate. The aqueous phase was extracted with ethyl acetate. The combined organic layers were washed with a saturated aqueous sodium chloride solution, dried over anhydrous sodium sulfate, filtered and concentrated in vacuo. Chromatography (1/15 ethyl acetate/petroleum ether) afforded 3-cyclopentyl-2-(4,5-dichloro-6-oxo-6H-pyridazin-1-yl)-propionic acid methyl ester (23 g, 46.8%).
Workup
- stirringstirred at 25° C. for 1 h
- stirringwas stirred for 2 d at 50° C
- customThe reaction solution was partitioned between water and ethyl acetate
- extractionThe aqueous phase was extracted with ethyl acetate
- washThe combined organic layers were washed with a saturated aqueous sodium chloride solution
- dry with materialdried over anhydrous sodium sulfate
- filtrationfiltered
- concentrationconcentrated in vacuo
Sources & evidence
- ORD record
- ord-678b7651e6204f0e82d988ed90cfe5bf
- Source dataset
- uspto-grants-2012_09
- Patent number
- US08258134B2
Reaction notes
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