反应详情

温度

0 °C

To sodium hexamethyldisilazane (0.945M in tetrahydrofuran) (667 mL, 0.63 mol) in tetrahydrofuran (0.9 L) at -78° C., under nitrogen, was added a solution of ethyl 4,4,4-trifluorobutyrate (90.6 mL) in tetrahydrofuran (100 mL). After stirring for 1.5 hour, to the vigorously stirred mixture was added methyl iodide (112 mL) as fast as possible. The reaction was warmed with a 0° C. bath for 2 hours. Methanol (1 L) and 1N lithium hydroxide (1.2 L) were added and stirring continued for 48 hours. The mixture was acidified with 2N hydrochloric acid and extracted with ethyl acetate. The combined organic phase was washed (brine), dried (MgSO4), and evaporated at 30° C. After combination with product from separate conversions of ethyl 4,4,4-trifluorobutyrate (97.79 g), distillation afforded 2-methyl-4,4,4-trifluorobutyric acid (173.24 g, 96%) as a brown solid-liquid contaminated with 4,4,4-trifluorobutyric acid and 2,2-dimethyl-4,4,4-trifluorobutyric acid; bp 48.0°-108° C. (9,900 Pa); GLC: tR =6.1 min.

1. stirringstirring
2. waitcontinued for 48 hours
3. extractionextracted with ethyl acetate
4. washThe combined organic phase was washed (brine)
5. dry with materialdried (MgSO4)
6. customevaporated at 30° C
7. customAfter combination with product from separate
8. distillationconversions of ethyl 4,4,4-trifluorobutyrate (97.79 g), distillation