HCID 86588492, compound → HCID 12991326, compound

HRID 1862530Notes

Reaction equation

HRID 1862530 reaction equation
C[O:2][C:3](=[O:43])[C@@H:4](OCC1C=CC=CC=1)[CH2:5][N:6](N=C=O)[C:7]([C@@H:9]1[CH2:14][CH2:13][CH2:12][N:11]([C:15](=[O:31])[CH2:16][CH2:17][CH:18]2[CH2:23][CH2:22][N:21]([C:24]([O:26][C:27]([CH3:30])([CH3:29])[CH3:28])=[O:25])[CH2:20][CH2:19]2)[CH2:10]1)=[O:8]>CO.[Pd]>[C:27]([O:26][C:24]([N:21]1[CH2:22][CH2:23][CH:18]([CH2:17][CH2:16][C:15]([N:11]2[CH2:12][CH2:13][CH2:14][C@@H:9]([C:7]([NH:6][CH2:5][C@H:4]([NH:6][C:7](=[O:8])[CH3:9])[C:3]([OH:2])=[O:43])=[O:8])[CH2:10]2)=[O:31])[CH2:19][CH2:20]1)=[O:25])([CH3:30])([CH3:29])[CH3:28]

Participants

4

Reactant 1

HCID 86588492HCID 86588492, compound

Product 1

HCID 12991326HCID 12991326, compoundYield 197.2%

Reagents, catalysts & solvents 2

HCID 23938PalladiumCatalystHCID 887MethanolSolvent

Procedure

A mixture of N-[(R)-1-[3-(1-tert-butoxycarbonyl-4-piperidyl)propionyl]-3-piperidylcarbonyl]-2(S)-benzyloxy-carbonylamino-β-alanine methyl ester (20 g) and 10% Pd on carbon (50% wet) (5 g) in methanol (500 ml) was stirred vigorously under a hydrogen atmosphere (1 atm) at room temperature. After 2 hours, the insolved material was removed by filtration, and the filtrate was concentrated in vacuo. The residue was dissolved in tetrahydrofuran (200 ml), and cooled to 0° C. 1N aqueous LiOH (116 ml) solution was added to the solution within 15 minutes at 0-3° C. After the mixture was stirred for 45 minutes at 0° C., acetic anhydride (6.89 ml) was added to the mixture within 15 minutes at 0-4° C. The mixture was stirred for 30 minutes at 0° C., then diethyl ether (150 ml) was added. The aqueous layer was separated, and the pH of it was adjusted to 2.5 with aqueous 20% KHSO4 , then extracted with ethyl acetate. The extract was dried over Na2SO4, and concentrated in vacuo to give N-[(R)-1-[3-(1-tert-butoxycarbonyl-4-piperidyl)propionyl]-3-piperidylcarbonyl]-2(S)-acetylamino-β-alanine (16.3 g) as a colorless oil.

Workup

  1. customthe insolved material was removed by filtration
  2. concentrationthe filtrate was concentrated in vacuo
  3. dissolutionThe residue was dissolved in tetrahydrofuran (200 ml)
  4. temperaturecooled to 0° C
  5. addition1N aqueous LiOH (116 ml) solution was added to the solution within 15 minutes at 0-3° C
  6. stirringAfter the mixture was stirred for 45 minutes at 0° C.
  7. additionacetic anhydride (6.89 ml) was added to the mixture within 15 minutes at 0-4° C
  8. stirringThe mixture was stirred for 30 minutes at 0° C.
  9. additiondiethyl ether (150 ml) was added
  10. customThe aqueous layer was separated
  11. extractionextracted with ethyl acetate
  12. dry with materialThe extract was dried over Na2SO4
  13. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-0648fa15a6584c16817ef3f7f529d24d
Source dataset
uspto-grants-2003_03
Patent number
US06538007B1

Reaction notes

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