1,1'-Carbonyldiimidazole → Ethyl 3-(5-chloro-2-methoxyphenyl)-3-oxopropanoate
Reaction equation
[Cl:1][C:2]1[CH:3]=[CH:4][C:5]([O:11][CH3:12])=[C:6]([CH:10]=1)[C:7]([OH:9])=O.C1N=CN(C(N2C=NC=C2)=O)C=1.[C:25]([O:31][CH2:32][CH3:33])(=[O:30])[CH2:26]C([O-])=O.[K+].[Cl-].[Mg+2].[Cl-]>O1CCCC1>[Cl:1][C:2]1[CH:3]=[CH:4][C:5]([O:11][CH3:12])=[C:6]([C:7](=[O:9])[CH2:26][C:25]([O:31][CH2:32][CH3:33])=[O:30])[CH:10]=1Participants
Procedure
To a stirring solution of 5-chloro-2-methoxybenzoic acid (1.87 g, 10.0 mmol, 1 eq) in 20 mL tetrahydrofuran was added N,N-carbonyldiimidazole (1.64 g, 10.1 mmol, 1.01 eq), and stirring was continued for twenty minutes to generate the acyl-imidazole. Separately, potassium ethyl malonate (4.08 g, 24.0 mmol, 2.39 eq) and magnesium chloride (1.15 g, 12.1 mmol, 1.20 eq) were suspended in 20 mL tetrahydrofuran. To the magnesium chloride mixture was added the acyl-imidazole solution. Stirring was continued at 50° C. for 1.5 hours. The reaction mixture was partitioned between ethyl acetate and water, and the organic portion dried over magnesium sulfate, filtered through a pad of celite, and concentrated to provide ethyl 3-(5-chloro-2-methoxyphenyl)-3-oxopropanoate, which was used without further purification. LCMS (ESI) m+H=257.2
Workup
- waitwas continued for twenty minutes
- stirringStirring
- customThe reaction mixture was partitioned between ethyl acetate and water
- dry with materialthe organic portion dried over magnesium sulfate
- filtrationfiltered through a pad of celite
- concentrationconcentrated
Sources & evidence
- ORD record
- ord-6c45b99b5a6346c8952064ffffc1c3b8
- Source dataset
- uspto-grants-2015_04
- Patent number
- US08999998B2
Reaction notes
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