Sodium borohydride → 1,1-Dimethylethyl 6-cyano-3,5-dihydroxyhexanoate

Temperatur

25 °C

Crude 5R 1,1-dimethylethyl 6-cyano-5-hydroxy-3-oxohexanoate (about 130 mmoles) from Step (1) is dissolved in the first distillate from the above Step (a) mixture and cooled to −75° C.±20° C. Sodium borohydride (6 g) as a solution in 75 mL triglyme is added slowly. After the addition, the reaction mixture is warmed to 25° C. The reaction mixture is quenched by the addition of 8 g acetic acid (and optionally 20 mL methanol) and concentrated by vacuum distillation—saving the distillate. The residue is dissolved in a mixture of water (100 mL) and ethyl acetate (200 mL), the layers separated, and the organic layer is concentrated by vacuum distillation. The residue is dissolved with 200 mL methanol and 10 mL acetic acid and concentrated by vacuum distillation. The residue is dissolved with 200 mL methanol and concentrated by vacuum distillation. The residue is dissolved with 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. customThe reaction mixture is quenched by the addition of 8 g acetic acid (and optionally 20 mL methanol) and
4. concentrationconcentrated by vacuum distillation—saving the distillate
5. dissolutionThe residue is dissolved in a mixture of water (100 mL) and ethyl acetate (200 mL)
6. customthe layers separated
7. concentrationthe organic layer is concentrated by vacuum distillation
8. dissolutionThe residue is dissolved with 200 mL methanol and 10 mL acetic acid
9. concentrationconcentrated by vacuum distillation
10. dissolutionThe residue is dissolved with 200 mL methanol
11. concentrationconcentrated by vacuum distillation
12. dissolutionThe residue is dissolved with 200 mL methanol
13. concentrationconcentrated by vacuum distillation
14. dissolutionThe residue is dissolved in ethyl acetate
15. concentrationconcentrated by vacuum distillation

ORD-Eintrag

ord-fc11ecaebe844ec6a6f6f4ee553274f2

Quelldatensatz

uspto-grants-2005_11

DOI

10.6084/m9.figshare.5104873.v1

Patentnummer

US06962994B2