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

HRID 1358709Notes

Reaction equation

HRID 1358709 reaction equation
[C:1]([CH2:3][CH:4]([OH:16])[CH2:5][C:6](=[O:15])[CH2:7][C:8]([O:10][C:11]([CH3:14])([CH3:13])[CH3:12])=[O:9])#[N:2].[BH4-].[Na+]>COCCOCCOCCOC>[C:1]([CH2:3][CH:4]([OH:16])[CH2:5][CH:6]([OH:15])[CH2:7][C:8]([O:10][C:11]([CH3:12])([CH3:14])[CH3:13])=[O:9])#[N:2]

Participants

4

Reactant 2

HCID 4311764Sodium borohydrideHCID 11637184Tert-butyl 6-cyano-5-hydroxy-3-oxohexanoate

Product 1

HCID 222829971,1-Dimethylethyl 6-cyano-3,5-dihydroxyhexanoate

Reagents, catalysts & solvents 1

HCID 8189TriglymeSolvent

Procedure

Crude 5R 1,1-dimethylethyl 6-cyano-5-hydroxy-3-oxohexanoate (about 150 mmoles) is dissolved in the first distillate from the above mixture, allowed to stir at room temperature for about 2 hours, and cooled to about −70° C. Sodium borohydride (6 g) as a solution in 75 mL triglyme 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. The residue is diluted with methanol and concentrated by vacuum distillation. 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 with 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.

Workup

  1. temperaturecooled to about −70° 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
  6. additionThe residue is diluted with methanol
  7. concentrationconcentrated by vacuum distillation
  8. dissolutionThe residue is dissolved in a mixture of water and ethyl acetate
  9. customthe layers separated
  10. concentrationthe organic layer is concentrated by vacuum distillation
  11. dissolutionThe residue is dissolved with methanol and acetic acid
  12. concentrationconcentrated by vacuum distillation
  13. dissolutionThe residue is dissolved in ethyl acetate
  14. concentrationconcentrated by vacuum distillation

Sources & evidence

ORD record
ord-8662f5eee7c4460f977171045eb19a8d
Source dataset
uspto-grants-2003_07
Patent number
US06596879B2

Reaction notes

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