p-Toluenesulfonic acid → HCID 131713519, compound

HRID 1262622Notes

Reaction equation

HRID 1262622 reaction equation
[NH2:1][CH2:2][CH2:3][CH2:4][CH2:5][CH:6]([CH2:24][P:25]([O:37]COC(=O)C(C)(C)C)([CH2:27][CH2:28][CH2:29][CH2:30][C:31]1[CH:36]=[CH:35][CH:34]=[CH:33][CH:32]=1)=[O:26])[CH2:7][N:8]1[CH2:23][CH2:22][CH2:21][C@H:9]1[C:10]([O:12][CH2:13][O:14][C:15](=[O:20])[C:16]([CH3:19])([CH3:18])[CH3:17])=[O:11].CC1C=CC(S(O)(=O)=[O:54])=CC=1>CO.C(O)(=O)C.[Pd]>[NH2:1][CH2:2][CH2:3][CH2:4][CH2:5][CH:6]([CH2:24][P:25]([OH:37])([CH2:27][CH2:28][CH2:29][CH2:30][C:31]1[CH:36]=[CH:35][CH:34]=[CH:33][CH:32]=1)=[O:26])[C:7]([N:8]1[CH2:23][CH2:22][CH2:21][C@H:9]1[C:10]([O:12][CH2:13][O:14][C:15](=[O:20])[C:16]([CH3:19])([CH3:18])[CH3:17])=[O:11])=[O:54]

Participants

6

Reactant 2

HCID 6101p-Toluenesulfonic acidHCID 131713520HCID 131713520, compound

Product 1

HCID 131713519HCID 131713519, compoundYield 75%

Reagents, catalysts & solvents 3

HCID 23938PalladiumCatalystHCID 176Acetic AcidSolventHCID 887MethanolSolvent

Procedure

A solution of 0.800 g (1.16 mmol) of (±)-1-[6-amino-2-[[[(2,2-dimethyl-1-oxopropoxy)methoxy](4-phenylbutyl)phosphinyl]methyl]hexyl]-L-proline, (2,2-dimethyl-1-oxopropoxy)methyl ester, 4-methylbenzenesulfonic acid (1:1) salt (prepared as described in Example 12) in a mixture of 15 ml of methanol and 1 ml of acetic acid was cooled in an ice-water bath under argon and treated with 250 mg of 10% Pd-C. The reaction mixture was subjected to a slow flow of H2 at 1 atm for 31/2 hours, then filtered and concentrated in vacuo to 0.710 g of residue which was purified by reverse phase gradient elution chromatography on a 25×250 mm HP-20 column (500 ml H2O to 500 ml CH3CN, linear gradient at ca. 4 ml/min flow). The product containing fractions were pooled and lyophilized to yield 0.476 g (75%) of the title product isolated as a 0.9 H2O solvate.

Workup

  1. temperaturewas cooled in an ice-water bath under argon
  2. custom2 hours
  3. filtrationfiltered
  4. concentrationconcentrated in vacuo to 0.710 g of residue which
  5. customwas purified by reverse phase gradient elution chromatography on a 25×250 mm HP-20 column (500 ml H2O to 500 ml CH3CN, linear gradient at ca. 4 ml/min flow)
  6. additionThe product containing fractions

Sources & evidence

ORD record
ord-6d3c0936878f4417943e6799b27842e9
Source dataset
uspto-grants-1984_06
Patent number
US04452791

Reaction notes

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