Water → HCID 86594266, compound

Participants

Reaction Conditions

Reaction Steps

A dry 250 mL round-bottom flask was equipped with a stir bar and flushed with Ar. Dry THF was added (40 mL) followed by addition of a 1.0 M solution of KO-t-Bu (37.5 mL, 37.5 mmol, 1.2 equiv). The solution was cooled to −78° C. in a dry-ice/acetone bath. Methyl isocyanoacetate (3.12 mL, 34.4 mmol, 1.0 equiv) was added dropwise over a 10 min period. The resulting mixture was stirred an additional 5 min followed by addition of 2,2,3,3-tetramethyl-butanal (4.0 g, 31.2 mmol, 1.0 equiv) via syringe. The cold-bath was removed and resulting mixture was stirred at room temperature for 1 h. The reaction mixture was diluted by addition of a mixture of 125 mL Et2O, 20 g ice and 2 mL AcOH. After the ice melted, 50 mL of water was added and the layers were mixed and separated. The organic layer was washed with 1×50 mL sat. NaHCO3 and dried over Na2SO4. The organic layer was decanted and concentrated. The crude enamide was purified by flash chromatography on silica gel using CH2Cl2 to 4% MeOH in CH2Cl2 to provide 2-formylamino-4,4,5,5-tetramethyl-hex-2-enoic acid ethyl ester as a thick oil (5.26 g, 74%); m/z calculated for C12H21NO3 227.3, found 228.3 (M+H)+.

Provenance & Evidence