Methanol → HCID 53432669, compound

HRID 2181397Notes

Reaction equation

HRID 2181397 reaction equation
[C:1]([C:3](=[CH:10][CH:11]([CH3:13])[CH3:12])[CH2:4][C:5]([O:7]CC)=[O:6])#[N:2].CO.[OH-].[K+]>O>[C:1]([C:3](=[CH:10][CH:11]([CH3:13])[CH3:12])[CH2:4][C:5]([OH:7])=[O:6])#[N:2]

Participants

5

Reactant 3

HCID 887MethanolHCID 14797Potassium HydroxideHCID 85054034Ethyl 3-cyano-5-methyl-3-hexenoate

Product 1

HCID 53432669HCID 53432669, compound

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Conditions

Temperature
55 °C

Procedure

A glass liner is charged with ethyl 3-cyano-5-methylhex-3-enoate (starting material prepared above), methanol (100 mL), and water (18 mL). Potassium hydroxide is added with stirring. A liner is placed in a 600 mL PARR hydrogenation vessel. The vessel is purged with nitrogen and then with hydrogen via charging to 60 psi and releasing the pressure on 5 cycles. The vessel is heated to 55° C. A solution of [(R,R)-MeDuPHOS]Rh(COD)+BF4− in deoxygenated methanol (18.0 mg in 20 mL) is added via syringe. The vessel is again purged with hydrogen and then pressurized to 60 psi with stirring. Periodically, hydrogen is added to maintain the pressure between 50 to 60 psi. Hydrogen uptake ceases after 5 hours. After an additional 1 hour, the mixture is cooled to room temperature, and the pressure is released. The mixture is transferred to a flask, and the solvent is removed in vacuo to give the product. A small sample is removed and converted to (S)-3-cyano-5-methylhexanoic acid by reaction with 1N hydrochloric acid. GC analysis shows 98.7% conversion to the desired cyano alkanoic salt with 96.6% e.e S isomer.

Workup

  1. customThe vessel is purged with nitrogen
  2. additionA solution of [(R,R)-MeDuPHOS]Rh(COD)+BF4− in deoxygenated methanol (18.0 mg in 20 mL) is added via syringe
  3. customThe vessel is again purged with hydrogen
  4. stirringwith stirring
  5. additionPeriodically, hydrogen is added
  6. temperatureto maintain the pressure between 50 to 60 psi
  7. waitAfter an additional 1 hour
  8. temperaturethe mixture is cooled to room temperature
  9. customThe mixture is transferred to a flask
  10. customthe solvent is removed in vacuo
  11. customto give the product
  12. customA small sample is removed
  13. customconverted to (S)-3-cyano-5-methylhexanoic acid by reaction with 1N hydrochloric acid

Sources & evidence

ORD record
ord-ebf446948945418aa31f8acf4eb06076
Source dataset
uspto-grants-2005_05
Patent number
US06891059B2

Reaction notes

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