Ethyl Acetate → Ethyl (3R)-4-cyano-3-hydroxybutanoate

HRID 610633Notes

Reaction equation

HRID 610633 reaction equation
[C-:1]#[N:2].[Na+].Br[CH2:5][C@H:6]([OH:13])[CH2:7][C:8]([O:10][CH2:11][CH3:12])=[O:9].C(OCC)(=O)C>O.C(O)C>[C:1]([CH2:5][C@@H:6]([OH:13])[CH2:7][C:8]([O:10][CH2:11][CH3:12])=[O:9])#[N:2]

Participants

6

Reactant 3

HCID 8857Ethyl AcetateHCID 8929Sodium CyanideHCID 12408095Ethyl (R)-(+)-4-bromo-3-hydroxybutyrate

Product 1

HCID 2733879Ethyl (3R)-4-cyano-3-hydroxybutanoateYield 59.8%

Reagents, catalysts & solvents 2

HCID 702EthanolSolventHCID 962WaterSolvent

Procedure

To a 50 gallon reactor containing a solution of 2.2 kg (44 mol) of sodium cyanide dissolved in 40 L of demineralized water was added 7 kg (33 mol) of (S)-4-bromo-3-hydroxybutyric acid, ethyl ester (Example 3) dissolved in 8 L of ethanol. The reaction mixture was stirred for 16 hours at room temperature. Ethyl acetate (65 L) was added, the mixture agitated, and the layers were allowed to separate. The lower aqueous layer was transferred to a 50 gallon vessel containing 2.5 kg of sodium chloride and 65 L of ethyl acetate, the mixture was agitated and the layers allowed to separate, and the lower aqueous layer was cut off. The organic layers were combined and concentrated in vacuo. The residue was distilled to afford 3.1 kg of the title compound; bp 110-125° C. 0.5 mm Hg; optical rotation [α]D25 =33.1° (C=1.08, chloroform);

Workup

  1. stirringthe mixture agitated
  2. customto separate
  3. customThe lower aqueous layer was transferred to a 50 gallon vessel
  4. additioncontaining 2.5 kg of sodium chloride and 65 L of ethyl acetate
  5. stirringthe mixture was agitated
  6. customto separate
  7. concentrationconcentrated in vacuo
  8. distillationThe residue was distilled

Sources & evidence

ORD record
ord-a5e5910e00c0485582a652197f61f684
Source dataset
uspto-grants-1999_12
Patent number
US05998633

Reaction notes

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