反应详情

温度

-55 °C

To a vessel containing 265 kg of 16.8% n-butyllithium is added a mixture of 80 kg of diisopropylamine in 80 L of tetrahydrofuran maintaining the temperature at less than 20° C. The solution is cooled to −55° C., and 85 kg of tert-butyl acetate is added maintaining the temperature at −50°±5° C. A solution of 25 kg of R 4-cyano-3-hydroxybutanoic acid ethyl ester in 55 L of tetrahydrofuran is then added, and the temperature is allowed to warm to −20° C. for at least 20 minutes. The solution is then quenched by transferring to aqueous hydrochloric acid. The organic layer is separated and the aqueous layer re-extracted with ethyl acetate. The combined organic layers are concentrated by vacuum distillation to afford crude 5R 1,1-dimethylethyl 6-cyano-5-hydroxy-3-oxohexanoate.

1. additionis added
2. temperaturemaintaining the temperature at −50°±5° C
3. temperatureto warm to −20° C. for at least 20 minutes
4. customThe solution is then quenched
5. customThe organic layer is separated
6. extractionthe aqueous layer re-extracted with ethyl acetate
7. concentrationThe combined organic layers are concentrated by vacuum distillation