反应详情

Crude 5R 1,1-dimethylethyl 6-cyano-5-hydroxy-3-oxohexanoate (about 150 moles) from Step (1) is dissolved in the first distillate from Step (a) along with 50 L of tetrahydrofuran, cooled to −75° C.±20° C., and optionally diluted with 25 L of methanol, and 10 kg of acetic acid. Sodium borohydride (8 kg) as a solution in methanol and aqueous sodium hydroxide is added slowly. After the addition, the reaction mixture is warmed to 0° C.±25° C. The reaction mixture is quenched by the addition of 10 kg of acetic acid and 20 L of methanol and concentrated by vacuum distillation. The residue is dissolved in methanol and acetic acid, optionally diluted with water, and concentrated by vacuum distillation. The residue is dissolved in methanol and concentrated by vacuum distillation. The residue is dissolved in a mixture of water and ethyl acetate, and the aqueous layer separated. 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 affording 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 0° C.±25° C
4. customThe reaction mixture is quenched by the addition of 10 kg of acetic acid and 20 L of methanol
5. concentrationconcentrated by vacuum distillation
6. dissolutionThe residue is dissolved in methanol
7. additionacetic acid, optionally diluted with water
8. concentrationconcentrated by vacuum distillation
9. dissolutionThe residue is dissolved in methanol
10. concentrationconcentrated by vacuum distillation
11. dissolutionThe residue is dissolved in a mixture of water and ethyl acetate
12. customthe aqueous layer separated
13. concentrationThe organic layer is concentrated by vacuum distillation
14. dissolutionThe residue is dissolved in methanol
15. concentrationacetic acid and concentrated by vacuum distillation
16. dissolutionThe residue is dissolved in ethyl acetate
17. concentrationconcentrated by vacuum distillation