HCID 14127229, compound → HCID 14127232, compound

HRID 620038Notes

Reaction equation

HRID 620038 reaction equation
[CH3:1][N:2]([CH2:20][C:21](=[O:39])[C@@H:22]([NH:30][C:31]([N:33]1[CH2:38][CH2:37][CH2:36][CH2:35][CH2:34]1)=[O:32])[CH2:23][C:24]1[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=1)[C:3]([N:5]1[CH2:19][CH2:18][CH2:17][C@H:6]1[C:7]([O:9]CC1C=CC=CC=1)=[O:8])=[O:4].O.O1CCOCC1>CO.[OH-].[Pd+2].[OH-]>[CH3:1][N:2]([CH2:20][C:21](=[O:39])[C@@H:22]([NH:30][C:31]([N:33]1[CH2:38][CH2:37][CH2:36][CH2:35][CH2:34]1)=[O:32])[CH2:23][C:24]1[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=1)[C:3]([N:5]1[CH2:19][CH2:18][CH2:17][C@H:6]1[C:7]([OH:9])=[O:8])=[O:4]

Participants

5

Reactant 2

HCID 14127229HCID 14127229, compoundHCID 218864351,4-Dioxane--water (1/1)

Product 1

HCID 14127232HCID 14127232, compound

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 9942167Palladium hydroxideSolvent

Procedure

A suspension of the phenylmethyl ester product from part (g) (0.8 g., 1.5 mmole) in methanol and palladium hydroxide (20% on carbon) is hydrogenated at room temperature and atmospheric pressure for 30 minutes. The mixture is filtered, the solids are rinsed with methanol, and the filtrate is concentrated to give 0.42 g. of yellow oil. The residue is chromatographed on LPS-1 silica gel using an elution gradient of 3→10% acetic acid in chloroform. Fractions containing the desired material are combined and concentrated. The residue is dissolved in methanol/water, filtered, concentrated (methanol removed) and lyophilized to give a white solid. The material is rechromatographed on CC-4 silica gel using ethyl acetate as the eluant. Fractions containing the desired produced are combined and lyophilized from water/dioxane to give 1-[[methyl[(S)-2-oxo-4-phenyl-3-[(1-piperidinylcarbonyl)amino]butyl]amino]carbonyl]-L-proline as a white solid; m.p. 69°-72°; [α]D25 =-37° (c=0.2, methanol). TLC (silica gel; toluene:acetic acid, 4:1) Rf =0.18.

Workup

  1. customis hydrogenated at room temperature
  2. filtrationThe mixture is filtered
  3. washthe solids are rinsed with methanol
  4. concentrationthe filtrate is concentrated
  5. customto give 0.42 g
  6. customThe residue is chromatographed on LPS-1 silica gel using an elution gradient of 3→10% acetic acid in chloroform
  7. additionFractions containing the desired material
  8. concentrationconcentrated
  9. dissolutionThe residue is dissolved in methanol/water
  10. filtrationfiltered
  11. concentrationconcentrated
  12. custom(methanol removed)
  13. customto give a white solid
  14. customThe material is rechromatographed on CC-4 silica gel
  15. additionFractions containing the
  16. customdesired produced

Sources & evidence

ORD record
ord-46a099b66ec24b46b5b5c4d6b956141b
Source dataset
uspto-grants-1989_04
Patent number
US04818757

Reaction notes

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