Hydrochloric Acid → L-Alanyl-L-proline

HRID 21774Notes

Reaction equation

HRID 21774 reaction equation
[C:1]([N:6]1[CH2:13][CH2:12][CH2:11][C@H:7]1[C:8]([OH:10])=[O:9])(=[O:5])[C:2]([CH3:4])=O.Cl.[NH2:15]O.C([O-])(=O)C.[Na+].Cl>O.[Pd].C(O)C.O>[NH2:15][C@H:2]([C:1]([N:6]1[CH2:13][CH2:12][CH2:11][C@H:7]1[C:8]([OH:10])=[O:9])=[O:5])[CH3:4]

Participants

8

Reactant 4

HCID 313Hydrochloric AcidHCID 443297Hydroxyamine hydrochlorideHCID 517045Sodium AcetateHCID 10130260(S)-1-(2-Oxopropanoyl)pyrrolidine-2-carboxylic acid

Product 1

HCID 83525L-Alanyl-L-proline

Reagents, catalysts & solvents 3

HCID 23219155Palladium hydrateCatalystHCID 702EthanolSolvent2×HCID 962WaterSolvent

Procedure

N-pyruvyl-L-proline (0.085 g., 0.46 mmoles, 1.0 eq.), hydroxylamine hydrochloride (0.048 g., 0.69 mmoles, 1.5 eq.), sodium acetate (0.056 g., 0.69 mmoles, 1.5 eq.), and 2 mL water and 10 mL ethanol were added to a 25 mL flask. The suspension was heated to reflux for 2 h. The imine was transferred under nitrogen gas with 100 mL ethanol to a 250 mL Parr flask. Palladium hydroxide-on-carbon (0.02 g., 0.18 mmoles, 0.4 eq.) and hydrochloric acid (6 mL, 0.2 moles, 430 eq.) were added and nitrogen was bubbled through for 3 minutes (pH=0.1). The material was hydrogenated for 17 hours as described in Example 1, Part A, to produce a >99.5% diastereomeric excess of L-alanyl-L-proline. Isolation of the product from the reaction mixture can be accomplished by filtering the latter through Celite® , adjusting the pH to 4, and concentrating the resultant solution to one-half volume. The solid which forms is collected by filtration, and held under vacuum to remove any residue solvent.

Workup

  1. temperatureThe suspension was heated
  2. temperatureto reflux for 2 h
  3. customnitrogen was bubbled through for 3 minutes (pH=0.1)

Sources & evidence

ORD record
ord-892c6ccd17574bc5b2073928a86fb4b9
Source dataset
uspto-grants-1995_06
Patent number
US05424454

Reaction notes

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