反应详情

Crude 5R 1,1-dimethylethyl 6-cyano-5-hydroxy-3-oxohexanoate (about 130 mmoles) from Step (1) is dissolved in 100 mL 1 M triethylborane in THF and 65 mL tetrahydrofuran, stirred for about 2 hours at room temperature, then cooled to −75° C.±20° C., and diluted with 25 mL methanol. Sodium borohydride (6 g) as a solution in triglyme (75 mL) is added slowly. After the addition, the reaction mixture is warmed to 20° C. to 25° C. The reaction mixture is quenched by the addition of 20 mL methanol and 8 g acetic acid and concentrated by vacuum distillation—saving the distillate. The residue is diluted with 100 mL water and 200 mL ethyl acetate, agitated, and the phases separated. The organic layer is concentrated by vacuum distillation—keeping this distillate separate from the first one. The residue is dissolved in 200 mL methanol and 10 mL acetic acid and concentrated by vacuum distillation. The residue is dissolved in 200 mL methanol and concentrated by vacuum distillation. The residue is dissolved in 200 mL methanol and concentrated by vacuum distillation. The residue is dissolved in ethyl acetate and concentrated by vacuum distillation resulting in crude [R—(R*,R*)]-1,1-dimethylethyl 6-cyano-3,5-dihydroxyhexanoate.

1. temperaturecooled to −75° C.±20° C.
2. additionAfter the addition
3. temperaturethe reaction mixture is warmed to 20° C. to 25° C
4. customThe reaction mixture is quenched by the addition of 20 mL methanol and 8 g acetic acid
5. concentrationconcentrated by vacuum distillation—saving the distillate
6. additionThe residue is diluted with 100 mL water and 200 mL ethyl acetate
7. customthe phases separated
8. concentrationThe organic layer is concentrated by vacuum distillation—keeping
9. customthis distillate separate from the first one
10. dissolutionThe residue is dissolved in 200 mL methanol
11. concentration10 mL acetic acid and concentrated by vacuum distillation
12. dissolutionThe residue is dissolved in 200 mL methanol
13. concentrationconcentrated by vacuum distillation
14. dissolutionThe residue is dissolved in 200 mL methanol
15. concentrationconcentrated by vacuum distillation
16. dissolutionThe residue is dissolved in ethyl acetate
17. concentrationconcentrated by vacuum distillation