HCID 53348343, compound → HCID 25190012, compound

HRID 1667390Notes

Reaction equation

HRID 1667390 reaction equation
[K+].[C:2]([C@@H:4]([CH2:14][CH:15]([CH3:17])[CH3:16])[CH:5]([C:9]([O:11]CC)=[O:10])[C:6]([O-])=[O:7])#[N:3].[H][H]>[Ni]>[CH2:14]([CH:4]1[CH2:2][NH:3][C:6](=[O:7])[C@H:5]1[C:9]([OH:11])=[O:10])[CH:15]([CH3:17])[CH3:16]

Participants

4

Reactant 2

HCID 53348343HCID 53348343, compound2×HCID 178418361HCID 178418361, compound

Product 1

HCID 25190012HCID 25190012, compound

Reagents, catalysts & solvents 1

HCID 935NickelCatalyst

Procedure

A vessel was charged with an aqueous solution containing (3S)-3-cyano-2-ethoxycarbonyl-5-methyl-hexanoic acid potassium salt (Formula 23, 411 L from Example 2). Raney Nickel (50% aq solution, Sigma-Aldrich) was added to the mixture, and hydrogen gas was introduced into the vessel over a 20 h period to maintain a pressure of 50 psig in the vessel headspace throughout reaction. The hydrogenation reaction was monitored by H2 uptake and HPLC analysis (C18 column, 4.6 mm×150 mm, detection at 200 nm) of the vessel contents. Following reaction, the aqueous mixture was filtered to remove the Raney Ni catalyst. The pH of the concentrated solution was adjusted to 3.0 using 37% HCl (about 14 L). The resulting solution was extracted three times with EtOAc (50% v/v). The combined organic layers were concentrated under vacuum to afford (S)-4-isobutyl-2-oxo-pyrrolidine-3-carboxylic acid (Formula 10). MS m/z [M+H]+186.1130. 13C NMR (75 ppm, CDCl3) δ 175.67, 172.23, 54.09, 47.62, 43.69, 37.22, 26.31, 23.34, 22.54. Yield 40-42%; 97% ee.

Workup

  1. additionA vessel was charged with an aqueous solution
  2. additionwas introduced into the vessel over a 20 h period
  3. temperatureto maintain a pressure of 50 psig in the vessel headspace
  4. customthroughout reaction
  5. customThe hydrogenation reaction
  6. customreaction
  7. filtrationthe aqueous mixture was filtered
  8. customto remove the Raney Ni catalyst
  9. extractionThe resulting solution was extracted three times with EtOAc (50% v/v)
  10. concentrationThe combined organic layers were concentrated under vacuum

Sources & evidence

ORD record
ord-626513b43d8e42a5b0c9ce01dbae1f85
Source dataset
uspto-grants-2011_10
Patent number
US08044227B2

Reaction notes

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