HCID 70021505, compound → HCID 11056128, compound

HRID 1384457Notes

Reaction equation

HRID 1384457 reaction equation
[CH3:1][O:2][C:3]1[CH:8]=[CH:7][C:6]([C@@H:9]([NH:11][C:12]([C:18]2[CH:19]=[N:20][CH:21]=[CH:22][CH:23]=2)=[CH:13][C:14]([O:16][CH3:17])=[O:15])[CH3:10])=[CH:5][CH:4]=1>CO.C(OCC)(=O)C.[OH-].[OH-].[Pd+2]>[CH3:1][O:2][C:3]1[CH:8]=[CH:7][C:6]([C@@H:9]([NH:11][C@H:12]([C:18]2[CH:19]=[N:20][CH:21]=[CH:22][CH:23]=2)[CH2:13][C:14]([O:16][CH3:17])=[O:15])[CH3:10])=[CH:5][CH:4]=1

Participants

5

Reactant 1

HCID 70021505HCID 70021505, compound

Product 1

HCID 11056128HCID 11056128, compound

Reagents, catalysts & solvents 3

HCID 9942167Palladium hydroxideCatalystHCID 887MethanolSolventHCID 8857Ethyl AcetateSolvent

Procedure

The crude methyl N-[(S)-1-(4-methoxyphenyl)ethyl]-3-amino-3-(3-pyridyl)propenoate, (40.6 g, 130 mmol) was dissolved in methanol (200 mL) and mixed with 20% Pd(OH)2/C (4.1 g). The mixture was hydrogenated under atmospheric pressure for 30 h. The mixture was diluted with ethyl acetate (50 mL) and filtered through celite (20 g) to remove the catalyst. The celite was washed with hot (70° C.) ethyl acetate(200 mL). The combined filtrate was concentrated under reduced pressure to near dryness to an oily residue. Crude amine (27.5 g) was dissolved in hot ethyl acetate (40 mL). The resulting hot yellow solution was filtered and rinsed with 15 mL of hot ethyl acetate. The clear solution was concentrated to <50 mL and allowed to stand at room temperature overnight. The resulting white crystalline solid was collected by filtration and washed with cold ethyl acetate (EtOAc) (˜15-20 mL), then air dried. Yield of isolated solid: 15.5 g. HPLC analysis showed >99% desired diastereomer. A second crop was obtained from the filtrate after concentration to about 20 mL. Yield: 1.7 g identical by HPLC to first crop; total yield: 17.2 g (62.5%)

Workup

  1. filtrationfiltered through celite (20 g)
  2. customto remove the catalyst
  3. washThe celite was washed with hot (70° C.) ethyl acetate(200 mL)
  4. concentrationThe combined filtrate was concentrated under reduced pressure
  5. dissolutionCrude amine (27.5 g) was dissolved in hot ethyl acetate (40 mL)
  6. filtrationThe resulting hot yellow solution was filtered
  7. washrinsed with 15 mL of hot ethyl acetate
  8. concentrationThe clear solution was concentrated to <50 mL
  9. waitto stand at room temperature overnight
  10. filtrationThe resulting white crystalline solid was collected by filtration
  11. washwashed with cold ethyl acetate (EtOAc) (˜15-20 mL)
  12. customair dried
  13. customA second crop was obtained from the filtrate
  14. concentrationafter concentration to about 20 mL

Sources & evidence

ORD record
ord-c1bd8c9a92314412a092f11314b0e5df
Source dataset
uspto-grants-2001_07
Patent number
US06258956B1

Reaction notes

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