反应详情

温度

-78 °C

Lithium diisopropylamide (1.5 M solution in cyclohexane/THF/ethylbenzene) (113 mL, 169 mmol, 1.1 equiv) was syringed into a 1000 mL round-bottom flask under a blanket of Ar. Dry THF (150 mL) was added and the mixture was cooled to −78° C. with a dry-ice/acetone bath. 3-Methyl-butanoic acid ethyl ester (20 g, 23 mL, 154 mmol, 1.0 equiv) was added dropwise from a syringe over a 10 min period followed by stirring at −78° C. for 1 h. Methyl iodide (10.5 mL, 169 mmol, 1.1 equiv) was added dropwise from a syringe over a 10 min period and the creamy mixture was stirred for 1 h at −78° C., resulting in a very thick mixture. The dry-ice bath was removed and replaced with an ice bath at 0° C. Another 150 mL of dry THF was added followed by another addition of LDA (113 mL, 169 mmol, 1.1 equiv). The resulting mixture was stirred for 10 min and then the flask was re-immersed in a dry-ice/acetone bath. Stirring was continued for another 50 min and then methyl iodide was added dropwise (10.5 mL, 169 mmol, 1.1 equiv) and the dry-ice/acetone bath was removed and the resulting mixture was stirred at ambient temperature for 14 h. The reaction mixture was quenched with 3 mL of conc. HCl and 2 N HCl was added until the pH was adjusted to <1. The mixture was further diluted with 150 mL water and 500 mL Et2O. The layers were separated and the organic layer was washed with 2 N HCl (1×100 mL), saturated NaHCO3 (1×100 mL), and brine (1×200 nL). The organic layer was dried over Na2SO4 and then concentrated in vacuo to provide 2,2,3-trimethylbutanoic acid ethyl ester as an orange oil mixed with ethyl benzene (36.4 g of which 22.1 g was product by NMR). The mixture was used without further purification.

1. stirringthe creamy mixture was stirred for 1 h at −78° C.
2. customresulting in a very thick mixture
3. customThe dry-ice bath was removed
4. customreplaced with an ice bath at 0° C
5. additionAnother 150 mL of dry THF was added
6. stirringThe resulting mixture was stirred for 10 min
7. customthe flask was re-immersed in a dry-ice/acetone bath
8. stirringStirring
9. waitwas continued for another 50 min
10. customthe dry-ice/acetone bath was removed
11. stirringthe resulting mixture was stirred at ambient temperature for 14 h
12. customThe reaction mixture was quenched with 3 mL of conc. HCl and 2 N HCl
13. additionwas added until the pH
14. additionThe mixture was further diluted with 150 mL water and 500 mL Et2O
15. customThe layers were separated
16. washthe organic layer was washed with 2 N HCl (1×100 mL), saturated NaHCO3 (1×100 mL), and brine (1×200 nL)
17. dry with materialThe organic layer was dried over Na2SO4
18. concentrationconcentrated in vacuo