Hydrochloric Acid → (S)-2-amino-4,4-difluoro-5-phenyl-pentanoic acid methyl ester hydrochloride

HRID 1455567Notes

Reaction equation

HRID 1455567 reaction equation
[CH3:1][O:2][C:3](=[O:27])[C@@H:4]([NH:16]C(OCC1C=CC=CC=1)=O)[CH2:5][C:6]([F:15])([F:14])[CH2:7][C:8]1[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=1.O1CCOCC1.[ClH:34]>CO.[Pd]>[ClH:34].[CH3:1][O:2][C:3](=[O:27])[C@@H:4]([NH2:16])[CH2:5][C:6]([F:15])([F:14])[CH2:7][C:8]1[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=1

Participants

6

Reactant 3

HCID 313Hydrochloric AcidHCID 312751,4-DioxaneHCID 57535357Methyl (S)-2-benzyloxycarbonylamino-4,4-difluoro-5-phenylpentanoate

Product 1

HCID 68820868(S)-2-amino-4,4-difluoro-5-phenyl-pentanoic acid methyl ester hydrochlorideYield 85.5%

Reagents, catalysts & solvents 2

HCID 23938PalladiumCatalyst2×HCID 887MethanolSolvent

Procedure

A solution of (S)-2-benzyloxycarbonylamino-4,4-difluoro-5-phenyl-pentanoic acid methyl ester (7.806 g, 20.68 mmol) in 120 mL of methanol and 4 M HCl in dioxane (41.4 mmol, 10.3 mL) is hydrogenated over 10% Pd/C (1.0 g) at 50 psi. After 8 hr, another portion of 10% Pd/C (1.0 g) is added. After 24 hr, the catalyst is removed by filtration over a pad of Celite, and the filtrate is concentrated in vacuum. The resulting solid is dissolved in a minimum amount of methanol and slowly added to ether (150 mL). The resulting slurry is aged for 30 min and then filtered. The solid is dried under suction to afford (S)-2-amino-4,4-difluoro-5-phenyl-pentanoic acid methyl ester hydrochloride (4.950 g, 85.5%).

Workup

  1. waitAfter 24 hr
  2. customthe catalyst is removed by filtration over a pad of Celite
  3. concentrationthe filtrate is concentrated in vacuum
  4. dissolutionThe resulting solid is dissolved in a minimum amount of methanol
  5. additionslowly added to ether (150 mL)
  6. waitThe resulting slurry is aged for 30 min
  7. filtrationfiltered
  8. customThe solid is dried under suction

Sources & evidence

ORD record
ord-5208bef08b2f4244b4ed59c066f45dec
Source dataset
uspto-grants-2009_01
Patent number
US07482448B2

Reaction notes

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