反应详情

Crude 5R 1,1-dimethylethyl 6-cyano-5-hydroxy-3-oxohexanoate (about 150 mmoles) is dissolved by adding 22 mL diethylmethoxyborane and 200 mL tetrahydrofuran. The solution is stirred for about 2 hours at room temperature, then cooled to −70° C. to −75° C., and further diluted with 25 mL methanol. Sodium borohydride (6 g) as a solution in triglyme (75 mL) is added slowly at between −65° C. to −75° C. After the addition, the reaction mixture is warmed to 15° C. to 25° C., quenched by the addition of acetic acid and concentrated by vacuum distillation—keeping this distillate. The residue is diluted with methanol and concentrated by vacuum distillation—keeping this distillate and all subsequent ones separate from the first one. The residue is dissolved in a mixture of water and ethyl acetate, the layers separated, and the organic layer is concentrated by vacuum distillation. The residue is dissolved in methanol and acetic acid 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 −70° C. to −75° C.
2. additionAfter the addition
3. temperaturethe reaction mixture is warmed to 15° C. to 25° C.
4. customquenched by the addition of acetic acid
5. concentrationconcentrated by vacuum distillation—keeping this distillate
6. additionThe residue is diluted with methanol
7. concentrationconcentrated by vacuum distillation—keeping this distillate
8. customall subsequent ones separate from the first one
9. dissolutionThe residue is dissolved in a mixture of water and ethyl acetate
10. customthe layers separated
11. concentrationthe organic layer is concentrated by vacuum distillation
12. dissolutionThe residue is dissolved in methanol
13. concentrationacetic acid and concentrated by vacuum distillation
14. dissolutionThe residue is dissolved in ethyl acetate
15. concentrationconcentrated by vacuum distillation