Acetic Acid → 1,1-Dimethylethyl 6-cyano-3,5-dihydroxyhexanoate

HRID 466295Notes

Reaction equation

HRID 466295 reaction equation
[C:1]([CH2:3][C@@H: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].COB(CC)CC.[BH4-].[Na+].C(O)(=O)C>O1CCCC1.C(OCC)(=O)C.CO>[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

8

Reactant 4

HCID 176Acetic AcidHCID 522516DiethylmethoxyboraneHCID 4311764Sodium borohydrideHCID 9794547tert-Butyl (R)-6-Cyano-5-hydroxy-3-oxohexanoate

Product 1

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

Reagents, catalysts & solvents 3

HCID 887MethanolSolventHCID 8028TetrahydrofuranSolvent2×HCID 8857Ethyl AcetateSolvent

Conditions

Temperature
-85 °C

Procedure

Crude (5R)-1,1-dimethylethyl 6-cyano-5-hydroxy-3-oxo-hexanoate (Example 1), approximately 52 mol, is dissolved in 90 L of tetrahydrofuran and 19 L of methanol under a nitrogen atmosphere. This solution is cooled to -85° C. and 24 L of a 50% solution of methoxydiethylborane in tetrahydrofuran is added. The reaction is cooled to -97° C. and 3.6 kg (126 mol) of sodium borohydride is added in 0.2 kg portions over 3 hours. The reaction is maintained between -93° C. and -85° C. for 5 hours and allowed to warm to room temperature and stand for 10 hours under a nitrogen atmosphere. The reaction is quenched by the addition of 7.5 L (118.5 mol) of acetic acid and concentrated by vacuum distillation to an oil. The residue is dissolved with 40 L of methanol, concentrated by vacuum distillation, redissolved with 44 L of methanol and reconcentrated by vacuum distillation to give a brown oil. This oil is taken up in 90 L of ethyl acetate and washed with 30 L of deionized water. The ethyl acetate solution is concentrated by vacuum distillation to give the title compound, [R-(R*,R*)]-1,1-dimethylethyl 6-cyano-3,5-dihydroxyhexanoate, which is used without further purification.

Workup

  1. temperatureThe reaction is cooled to -97° C.
  2. temperatureThe reaction is maintained between -93° C. and -85° C. for 5 hours
  3. temperatureto warm to room temperature
  4. concentrationconcentrated by vacuum distillation to an oil
  5. dissolutionThe residue is dissolved with 40 L of methanol
  6. concentrationconcentrated by vacuum distillation
  7. dissolutionredissolved with 44 L of methanol
  8. distillationreconcentrated by vacuum distillation
  9. customto give a brown oil
  10. washwashed with 30 L of deionized water
  11. concentrationThe ethyl acetate solution is concentrated by vacuum distillation

Sources & evidence

ORD record
ord-8fca21e3373f411bac67c6887bc1856f
Source dataset
uspto-grants-1992_10
Patent number
US05155251

Reaction notes

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