反应详情

温度

50 °C

To a solution of lithium bis(trimethylsilyl)amide in (154.48 g, 0.923 mol) in tetrahydrofuran (350 mL) was added 2-phenyl propionic acid (50.0 g, 0.333 mol) over 27 minutes maintaining the temperature below 25° C. Following a THF rinse (35 mL), the solution was heated to 50° C. for 23 minutes. The solution was then cooled below 25° C. and 3,3-dimethyl-1-iodobutane (110.3 g, 0.416 mol) was added. The reaction mixture was heated to 60° C. for 31 h, then was cooled to RT, and concentrated to a thick oil. Water (500 mL) was added and the solution was cooled to 10-15° C. and the pH was adjusted to <2 by the addition of 6 N HCl (75.59 g). The product was extracted with ethyl acetate (440 mL) and the organic layer was washed with 10% NaCl. The crude ethyl acetate solution (assayed for 66.8 g of 49-1, 85.6%) was concentrated to a thick oil and used in the resolution.

1. temperaturemaintaining the temperature below 25° C
2. washrinse (35 mL)
3. temperatureThe solution was then cooled below 25° C.
4. temperatureThe reaction mixture was heated to 60° C. for 31 h
5. temperaturewas cooled to RT
6. concentrationconcentrated to a thick oil
7. additionWater (500 mL) was added
8. temperaturethe solution was cooled to 10-15° C.
9. additionthe pH was adjusted to <2 by the addition of 6 N HCl (75.59 g)
10. extractionThe product was extracted with ethyl acetate (440 mL)
11. washthe organic layer was washed with 10% NaCl
12. concentrationThe crude ethyl acetate solution (assayed for 66.8 g of 49-1, 85.6%) was concentrated to a thick oil