N-(methoxycarbonyl)-trans-4-hydroxy-L-proline methyl ester → N-(methoxycarbonyl)-trans-4-hydroxy-D-proline methyl ester

HRID 583008Notes

Reaction equation

HRID 583008 reaction equation
[CH3:1][O:2][C:3](=[O:14])[C@@H:4]1[CH2:8][C@@H:7]([OH:9])[CH2:6][N:5]1[C:10]([O:12][CH3:13])=[O:11].[CH3:15][O:16][C:17](=[O:28])[C@H:18]1[CH2:22][C@@H:21]([OH:23])[CH2:20][N:19]1[C:24]([O:26][CH3:27])=[O:25]>P([O-])([O-])([O-])=O.[K+].[K+].[K+]>[CH3:1][O:2][C:3](=[O:14])[C@@H:4]1[CH2:8][C@H:7]([OH:9])[CH2:6][N:5]1[C:10]([O:12][CH3:13])=[O:11].[CH3:15][O:16][C:17](=[O:28])[C@H:18]1[CH2:22][C@H:21]([OH:23])[CH2:20][N:19]1[C:24]([O:26][CH3:27])=[O:25]

Participants

5

Reactant 2

HCID 10375601N-(methoxycarbonyl)-trans-4-hydroxy-L-proline methyl esterHCID 21310449N-(methoxycarbonyl)-cis-4-hydroxy-D-proline methyl ester

Product 2

HCID 14890840N-(methoxycarbonyl)-cis-4-hydroxy-L-proline methyl esterYield 3%HCID 21310450N-(methoxycarbonyl)-trans-4-hydroxy-D-proline methyl esterYield 82.7%

Reagents, catalysts & solvents 1

HCID 62657Potassium Phosphate, TribasicSolvent

Procedure

A 5.0 mL aqueous solution containing 51 mM N-(methoxycarbonyl)-trans-4-hydroxy-L-proline methyl ester and 51 mM N-(methoxycarbonyl)-cis-4-hydroxy-D-proline methyl ester in 0.100M potassium phosphate (pH 7.0) was mixed with 50 mg/mL of Candida antartica lipase fraction B at 25° C. The reaction was analyzed by removal of a 0.200 mL sample and mixing with an equivalent volume of 0.100M propionic acid (HPLC internal standard) in water. The resulting solution was filtered through a 10K molecular weight cut-off filter to remove the enzyme and the filtrate analyzed by high pressure liquid chromatography on a HPX-87H column (Bio-Rad, 30 cm×7.8 mm) to determine the percent conversion of each isomer of the diastereomeric mixture, and the diastereomeric excess of the N-(methoxycarbonyl)-trans-4-hydroxy-D-proline methyl ester. After 24 h, a 93% diastereomeric excess of N-(methoxycarbonyl)-trans-4-hydroxy-D-proline methyl ester was obtained at 57% conversion of the diastereomeric mixture (3.0% N-(methoxycarbonyl)-cis-4-hydroxy-L-proline methyl ester and 82.7% N-(methoxycarbonyl)-trans-4-hydroxy-D-proline methyl ester remained).

Workup

  1. additionwas mixed with 50 mg/mL of Candida antartica lipase fraction B at 25° C
  2. customThe reaction was analyzed by removal of a 0.200 mL sample
  3. additionmixing with an equivalent volume of 0.100M propionic acid (HPLC internal standard) in water
  4. filtrationThe resulting solution was filtered through a 10K molecular weight
  5. filtrationcut-off filter
  6. customto remove the enzyme

Sources & evidence

ORD record
ord-0e732c2d695c4e67a998543fbe72da4c
Source dataset
uspto-grants-1999_07
Patent number
US05928933

Reaction notes

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