Dimethylformamide dimethyl acetal → 3-Isopropyl-4-dimethylamino-2-oxo-but-3-enoic acid ethyl ester
Reaction equation
[CH3:1][O:2][C:3](=[O:10])[C:4](=[O:9])[CH2:5][CH:6]([CH3:8])[CH3:7].CO[CH:13](OC)[N:14]([CH3:16])[CH3:15].O.[C:20]1(C)C=CC(S(O)(=O)=O)=CC=1>>[CH2:1]([O:2][C:3](=[O:10])[C:4](=[O:9])[C:5]([CH:6]([CH3:8])[CH3:7])=[CH:13][N:14]([CH3:16])[CH3:15])[CH3:20]Participants
Conditions
- Temperature
- 80 °C
Procedure
To a solution of 4-methyl-2-oxo-pentanoic acid methyl ester (3.8 g, 26 mmol) in N,N-dimethylformamide dimethyl acetal (7 mL, 52 mmol) is added p-toluenesulfonic acid monohydrate (30 mg). The mixture is stirred at 80° C. overnight. The reaction mixture is concentrated under reduced pressure to give 3-isopropyl-4-dimethylamino-2-oxo-but-3-enoic acid ethyl ester as an orange oil. To a solution of 3-isopropyl-4-dimethylamino-2-oxo-but-3-enoic acid ethyl ester and 2,6-dichlorophenylhydrazine hydrochloride (2.8 g, 13 mmol) in EtOH (40 mL) is added concentrated HCl (0.5 mL). The mixture is stirred at ambient temperature for 2 h followed by refluxing overnight. The reaction mixture is concentrated and the residue is partitioned between EtOAc and 1N HCl. The organic phase is dried (Na2SO4) and concentrated to a residue. The residue is purified by column chromatography (0-15% EtOAc in hexanes) to give the title compound as an oil (2.2 g, 52%). 1H NMR (CDCl3): δ 7.76 (s, 1H), 7.43 (d, 2H), 7.34 (dd, 1H), 3.75 (s, 3H), 3.48 (m, 1H), 1.32 (d, 6H).
Workup
- concentrationThe reaction mixture is concentrated under reduced pressure
Sources & evidence
- ORD record
- ord-4b80fd2abc9d489daa4d5beaee00c9bf
- Source dataset
- uspto-grants-2012_04
- Patent number
- US08153624B2
Reaction notes
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