ethyl (R)-2-tert-butoxycarbonylamino-5-(4-chlorophenyl)-5-oxopentanoate → (2R,5S)-5-(4-chlorophenyl)pyrrolidine-2-carboxylic acid ethyl ester

HRID 1677072Notes

Reaction equation

HRID 1677072 reaction equation
[CH2:1]([O:3][C:4](=[O:25])[C@H:5]([NH:17]C(OC(C)(C)C)=O)[CH2:6][CH2:7][C:8]([C:10]1[CH:15]=[CH:14][C:13]([Cl:16])=[CH:12][CH:11]=1)=O)[CH3:2]>Cl.C(OCC)(=O)C>[CH2:1]([O:3][C:4]([C@H:5]1[CH2:6][CH2:7][C@@H:8]([C:10]2[CH:15]=[CH:14][C:13]([Cl:16])=[CH:12][CH:11]=2)[NH:17]1)=[O:25])[CH3:2]

Participants

3

Reactant 1

HCID 67371186ethyl (R)-2-tert-butoxycarbonylamino-5-(4-chlorophenyl)-5-oxopentanoate

Product 1

HCID 67372413(2R,5S)-5-(4-chlorophenyl)pyrrolidine-2-carboxylic acid ethyl esterYield 39.5%

Reagents, catalysts & solvents 1

HCID 21866389Hydrogen chloride-ethyl acetateSolvent

Conditions

Temperature
-50 °C

Procedure

A 4 N hydrochloric acid/ethyl acetate solution (120 mL) was added to (R)-2-t-butoxycarbonylamino-5-(4-chlorophenyl)-5-oxovaleric acid ethyl ester (17.4 g). Stirring was continued for 3 hours at room temperature. The solvent was removed under a vacuum, and ethyl acetate and saturated sodium bicarbonate solution was added, and the organic layer was partitioned. The organic layer was washed with brine and was dried with magnesium sulfate. The solvent was removed under a vacuum, and methanol (200 mL) and acetic acid (50 mL) were added to the residue. The reaction solution was cooled to −50° C., and sodium borohydride (1.07 g) was added over 20 minutes. After stirring for 4 hours at −50° C. to room temperature, the resultant was stirred overnight at room temperature. Disodium hydrogenphosphate solution was added to the reaction solution, and the solvent was removed under a vacuum, Water and ethyl acetate were added, and the organic layer was partitioned. Saturated sodium bicarbonate solution was added to the organic layer, and stirring was continued for 1 hour at room temperature, and the organic layer was partitioned. The organic layer was washed with brine and was dried over anhydrous magnesium sulfate. The solvent was removed under a vacuum, and the residue was purified by silica gel column chromatography (heptane/ethyl acetate), and the title compound (4.71 g) was obtained.

Workup

  1. customThe solvent was removed under a vacuum, and ethyl acetate and saturated sodium bicarbonate solution
  2. additionwas added
  3. customthe organic layer was partitioned
  4. washThe organic layer was washed with brine
  5. dry with materialwas dried with magnesium sulfate
  6. customThe solvent was removed under a vacuum, and methanol (200 mL) and acetic acid (50 mL)
  7. additionwere added to the residue
  8. additionsodium borohydride (1.07 g) was added over 20 minutes
  9. stirringAfter stirring for 4 hours at −50° C. to room temperature
  10. stirringthe resultant was stirred overnight at room temperature
  11. additionDisodium hydrogenphosphate solution was added to the reaction solution
  12. customthe solvent was removed under a vacuum, Water and ethyl acetate
  13. additionwere added
  14. customthe organic layer was partitioned
  15. additionSaturated sodium bicarbonate solution was added to the organic layer
  16. stirringstirring
  17. waitwas continued for 1 hour at room temperature
  18. customthe organic layer was partitioned
  19. washThe organic layer was washed with brine
  20. dry with materialwas dried over anhydrous magnesium sulfate
  21. customThe solvent was removed under a vacuum
  22. customthe residue was purified by silica gel column chromatography (heptane/ethyl acetate)

Sources & evidence

ORD record
ord-6eec769759ab4e97a16db0812eb822d7
Source dataset
uspto-grants-2011_08
Patent number
US08008293B2

Reaction notes

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