(S)-4-azido-1-[[hydroxy(4-phenylbutyl)phosphinyl]acetyl]-L-proline → (S)-4-Amino-1-[[hydroxy(4-phenylbutyl)phosphinyl]acetyl]-L-proline

HRID 851432Notes

Reaction equation

HRID 851432 reaction equation
[N:1]([CH:4]1[CH2:8][N:7]([C:9](=[O:24])[CH2:10][P:11]([OH:23])([CH2:13][CH2:14][CH2:15][CH2:16][C:17]2[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=2)=[O:12])[C@H:6]([C:25]([OH:27])=[O:26])[CH2:5]1)=[N+]=[N-]>[Pd].O>[NH2:1][CH:4]1[CH2:8][N:7]([C:9](=[O:24])[CH2:10][P:11]([OH:23])([CH2:13][CH2:14][CH2:15][CH2:16][C:17]2[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=2)=[O:12])[C@H:6]([C:25]([OH:27])=[O:26])[CH2:5]1

Participants

4

Reactant 1

HCID 86738870(S)-4-azido-1-[[hydroxy(4-phenylbutyl)phosphinyl]acetyl]-L-proline

Product 1

HCID 70073067(S)-4-Amino-1-[[hydroxy(4-phenylbutyl)phosphinyl]acetyl]-L-prolineYield 40.1%

Reagents, catalysts & solvents 2

HCID 23938PalladiumCatalystHCID 962WaterSolvent2×

Procedure

A mixture of (S)-4-azido-1-[[hydroxy(4-phenylbutyl)phosphinyl]acetyl]-L-proline (0.8 g) acetic acid (about 20 ml) and 10% palladium on charcoal is hydrogenated on a Parr apparatus for 3 hours. The reaction mixture is filtered through Celite to remove the catalyst and the solvent is stripped leaving an oil. The oil is diluted with water and washed several times with ethyl acetate. The aqueous phase is lyophilized yielding 0.48 g of crude product as a solid. Crude product (400 mg) is run on a column of ion-exchange resin AG50X8 (about 30 ml), eluting first with water and then with a pyridine-acetic acid buffer (pH 6.5). The fractions containing the desired material are combined and evaporated leaving a glass, which is dissolved in water and lyophilized yielding 300 mg of the title compound having an optical rotation [α]D =-24.8° (c=10 mg/ml, methanol).

Workup

  1. filtrationThe reaction mixture is filtered through Celite
  2. customto remove the catalyst
  3. customthe solvent is stripped leaving an oil
  4. washwashed several times with ethyl acetate
  5. customThe aqueous phase is lyophilized yielding 0.48 g of crude product as a solid
  6. wash(about 30 ml), eluting first with water
  7. additionThe fractions containing the desired material
  8. customevaporated
  9. customleaving a glass, which

Sources & evidence

ORD record
ord-4568656bd4ca4146b6fad2c38852dc30
Source dataset
uspto-grants-1983_05
Patent number
US04384123

Reaction notes

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