Triethylamine → HCID 12069395, compound

HRID 2181401Notes

Reaction equation

HRID 2181401 reaction equation
[C:1]([C:3](=[CH:8][CH:9]([CH3:11])[CH3:10])[CH2:4][C:5]([OH:7])=[O:6])#[N:2].[H][H].C(N(CC)CC)C.C([C@@H](CC(C)C)CC(O)=O)#N>CO>[C:1]([CH:3]([CH2:8][CH:9]([CH3:11])[CH3:10])[CH2:4][C:5]([OH:7])=[O:6])#[N:2]

Participants

6

Reactant 4

HCID 8471Triethylamine3×HCID 9855540(S)-3-cyano-5-methylhexanoic acid3×HCID 53432669HCID 53432669, compound3×HCID 178418361HCID 178418361, compound3×

Product 1

HCID 12069395HCID 12069395, compoundYield 51%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent2×

Procedure

The above procedure was followed to react 250 mg (1.634 mmol) of 3-cyano-5-methylhex-3-enoic acid with hydrogen (50 psi) in the presence of 8 mg (0.01634 mmol) of [(S,S)-Et-BPE]Rh(COD)+BF4− and 0.023 mL (0.1634 mmol; 0.1 eq) of triethylamine in 5 mL of methanol at 24° C. for 40 hours. The reaction mixture was filtered, the solvent was removed by evaporation, and the product was shown by proton NMR to be 71% (S)-3-cyano-5-methylhexanoic acid with 84% e.e. for the S-enantiomer. C. The above procedure was repeated, except that no base was added to the reaction mixture. The product was shown by proton NMR to be 26%, (S)-3-cyano-5-methylhexanoic acid having 91% e.e. for the S-enantiomer. D. The above procedure was followed to react 200 mg (1.307 mmol) of 3-cyano-5-methylhex-3-enoic acid with hydrogen (50 psi, 100 hours) in the presence of 10 mg (0.01307 mmol) of [(S,S)-Et-DuPHOS]Rh(COD)+BF4−. The product was shown by proton NMR to be 82% (S)-3-cyano-5-methylhexanoic acid having 56% e.e. for the S-enantiomer. E. The procedure of Example 5D was repeated, except that 0.1 eq. (0.02 mL, 0.1307 mmol) of triethylamine was added to the reactive mixture. The reaction was stopped after 16 hours, and the product was shown to be 86% (S)-3-cyano-5-methylhexanoic acid with 68% e.e. for the S-enantiomer. F. The procedure of Example 5E was repeated, except that 1 eq. (0.18 mL, 1.307 mmol) of triethylamine was added to the reaction mixture, and the reaction was stopped at 16 hours. The product was shown by proton NMR to be 92% converted to (S)-3-cyano-5-methylhexanoic acid having 56% e.e. for the S-enantiomer. G. By following the general procedures from above, 250 mg (1.634 mmol) of 3-cyano-5-methylhex-3-enoic acid was reacted with hydrogen (50 psi, 16 hours. 24° C.) in the presence of 12 mg (0.01634 mmol) of [(R,R)-DIPAMP]Rh(COD)+BF4− in methanol (10 mL) to provide 51% of 3-cyano-5-methylhexanoic acid having 72% e.e. for the R-enantiomer.

Workup

  1. filtrationThe reaction mixture was filtered
  2. customthe solvent was removed by evaporation
  3. additionwas added to the reaction mixture
  4. additionwas added to the reactive mixture
  5. additionwas added to the reaction mixture
  6. waitthe reaction was stopped at 16 hours

Sources & evidence

ORD record
ord-ad8a38d7ef3f4094b028cc67d90872c4
Source dataset
uspto-grants-2005_05
Patent number
US06891059B2

Reaction notes

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