Diethyl Ether → Ethyl 2-formamido-4,4,5-trimethylhex-2-enoate

Temperatur

-78 °C

A clean and 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 (32.2 mL, 32.2 mmol, 1.05 equiv). The solution was cooled to −78° C. in a dry-ice/acetone bath. Ethyl isocyanoacetate (3.35 mL, 30.7 mmol, 1.0 equiv) was added dropwise over a 10 min period. The resulting mixture was stirred an additional 5 min followed by addition, via syringe, of 2,2,3-trimethyl-butanal (3.5 g, 30.7 mmol, 1.0 equiv). 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 mix of 125 mL Et2O, 20 g ice, 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-trimethyl-hex-2-enoic acid ethyl ester as a thick oil (4.54 g); MS: 228 (M+1).

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

ORD-Eintrag

ord-ff26910083a84cdb9adf4bd30435b734

Quelldatensatz

uspto-grants-2005_02

DOI

10.6084/m9.figshare.5104873.v1

Patentnummer

US06858623B2