Water → HCID 86594266, compound

Temperature

-78 °C

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)+.

1. customA dry 250 mL round-bottom flask was equipped with a stir bar
2. customflushed with Ar
3. additionDry THF was added (40 mL)
4. customThe cold-bath was removed
5. customresulting mixture
6. stirringwas stirred at room temperature for 1 h
7. additionthe layers were mixed
8. customseparated
9. washThe organic layer was washed with 1×50 mL sat. NaHCO3
10. dry with materialdried over Na2SO4
11. customThe organic layer was decanted
12. concentrationconcentrated
13. customThe crude enamide was purified by flash chromatography on silica gel

ORD record

ord-956933d988b54bc89eeae7f9ffd48d46

Source dataset

uspto-grants-2008_12

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07465745B2