2-Oxo-4-phenylbutyric acid → HCID 22822694, compound

HRID 1758868Notes

Reaction equation

HRID 1758868 reaction equation
O=[C:2]([CH2:6][CH2:7][C:8]1[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=1)[C:3]([OH:5])=[O:4].C(OC(N[NH:25][CH:26]([C:28]([N:30]1[CH2:37][CH2:36][CH2:35][C@H:31]1[C:32]([OH:34])=[O:33])=[O:29])[CH3:27])=O)C1C=CC=CC=1.C([BH3-])#[N:39].[Na+]>>[C:3]([CH:2]([NH:25][CH:26]([C:28]([N:30]1[CH2:37][CH2:36][CH2:35][C@H:31]1[C:32]([OH:34])=[O:33])=[O:29])[CH2:27][NH2:39])[CH2:6][CH2:7][C:8]1[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=1)([OH:5])=[O:4]

Participants

4

Reactant 3

HCID 697322-Oxo-4-phenylbutyric acidHCID 5003444Sodium cyanoborohydrideHCID 131712973benzyloxycarbonylamino-D,L-alanyl-L-proline

Product 1

HCID 22822694HCID 22822694, compound

Procedure

Under basic conditions, DL-α,β-diaminopropionic acid is reacted with excess benzyloxycarbonyl chloride to yield upon acidification D,L-α,β-bis(benzyloxycarbonylamino)-propionic acid (mp=123.5°-124° C. ). Phosphorous pentachloride is added to a chloroform solution containing the di-Cbz product to yield on workup D,L-4-(benzyloxycarbonylaminomethyl)-oxazolidin-2,5-dione. A solution of L-proline t-butyl ester in methylene chloride is added to the N-carboxyanhydride in tetrahydrofuran at -60° C. After overnight freezer storage, the mixture is stripped to dryness affording crude product. Trifluoroacetic acid effectively cleaves the t-butyl ester in 2 hours at room temperature resulting in a gross mixture of L-proline and β-benzyloxycarbonylamino-D,L-alanyl-L-proline. Gel filtration chromatography (LH-20) results in pure dipeptide. 2-Oxo-4-phenylbutyric acid and benzyloxycarbonylamino-D,L-alanyl-L-proline are condensed in the presence of sodium cyanoborohydride. Removal of the protecting group from the resulting product yields N-(1-carboxy-3-phenylpropyl)-β-amino-D,L-alanyl-L-proline. The nmr in D2O showed aromatic protons at 7.4δ, methine protons at 4.2δ and multiplets at 3.7, 3.2, 2.9 and 2.1δ.

Workup

  1. filtrationGel filtration chromatography (LH-20)
  2. customresults in pure dipeptide
  3. customRemoval of the protecting group from the resulting product

Sources & evidence

ORD record
ord-22481c768593470aa606a4dad46e4d56
Source dataset
uspto-grants-1983_02
Patent number
US04374829

Reaction notes

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