Ethyl alpha-oxobenzenebutanoate → N-[1-(R,S)-carboxy-3-phenylpropyl]-L-lysyl-(S)-2-pyrrolidineacetic acid

HRID 979838Notes

Reaction equation

HRID 979838 reaction equation
C([O:3][C:4](=[O:27])[CH2:5][C@@H:6]1[CH2:10][CH2:9][CH2:8][N:7]1[C:11](=[O:26])[C@H:12]([CH2:21][CH2:22][CH2:23][CH2:24][NH2:25])[NH:13]C(OC(C)(C)C)=O)C.C([O:30][C:31](=[O:42])[C:32](=O)[CH2:33][CH2:34][C:35]1[CH:40]=[CH:39][CH:38]=[CH:37][CH:36]=1)C>>[C:31]([CH:32]([NH:13][C@H:12]([C:11]([N:7]1[CH2:8][CH2:9][CH2:10][C@H:6]1[CH2:5][C:4]([OH:27])=[O:3])=[O:26])[CH2:21][CH2:22][CH2:23][CH2:24][NH2:25])[CH2:33][CH2:34][C:35]1[CH:36]=[CH:37][CH:38]=[CH:39][CH:40]=1)([OH:30])=[O:42]

Participants

3

Reactant 2

HCID 562087Ethyl alpha-oxobenzenebutanoateHCID 53706975N--BOC-L-lysyl-(S)-2-pyrrolidineacetic acid ethyl ester

Product 1

HCID 131715010N-[1-(R,S)-carboxy-3-phenylpropyl]-L-lysyl-(S)-2-pyrrolidineacetic acid

Procedure

The product of Step A above is condensed with 2-oxo-4-phenylbutyric acid ethyl ester by the procedure of Example 1, Step E. The diastereomers are separated by silica gel chromatography. The individual diastereomers are converted into the corresponding diacids by saponification as in Example 2 and the -BOC group is removed in hydrogen chloride in ethyl acetate by the procedure of Example 1, Step D. The resulting hydrochloride salt is converted to the free base by absorbing on a strong acid ion exchange resin (Dowex 50W; H+ cycle) and eluting with 3% pyridine in water. Freeze drying affords the desired product, and the S,S,S and R,S,S, diastereomers are separated using reverse phase HPLC.

Workup

  1. customThe diastereomers are separated by silica gel chromatography
  2. customthe -BOC group is removed in hydrogen chloride in ethyl acetate by the procedure of Example 1, Step D
  3. customby absorbing on a strong acid ion exchange resin (Dowex 50W; H+ cycle)
  4. washeluting with 3% pyridine in water
  5. customFreeze drying

Sources & evidence

ORD record
ord-59581d7069e54c00a22610ee723059fd
Source dataset
uspto-grants-1987_01
Patent number
US04634716

Reaction notes

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