Sodium Hydroxide → (3S)-1-(4-hydroxyphenyl)-5-oxopyrrolidine-3-carboxylic acid

HRID 858931Notes

Reaction equation

HRID 858931 reaction equation
C[O:2][C:3]([CH:5]1[CH2:9][C:8](=[O:10])[N:7]([C:11]2[CH:16]=[CH:15][C:14]([OH:17])=[CH:13][CH:12]=2)[CH2:6]1)=[O:4].[OH-].[Na+]>C([O-])(=O)C.[Mg+2].C([O-])(=O)C.CC1CCCCC1>[OH:17][C:14]1[CH:13]=[CH:12][C:11]([N:7]2[C:8](=[O:10])[CH2:9][C@H:5]([C:3]([OH:4])=[O:2])[CH2:6]2)=[CH:16][CH:15]=1

Participants

5

Reactant 2

HCID 14798Sodium Hydroxide3×HCID 2883518Methyl 1-(4-hydroxyphenyl)-5-oxopyrrolidine-3-carboxylate

Product 1

HCID 699443(3S)-1-(4-hydroxyphenyl)-5-oxopyrrolidine-3-carboxylic acidYield 45.9%

Reagents, catalysts & solvents 2

HCID 7962MethylcyclohexaneSolventHCID 8896Magnesium AcetateSolvent

Conditions

Temperature
28 °C

Procedure

8.00 g Polyethyleneglycol 6000 was dissolved in 150 mL (100 mM) magnesium acetate buffer pH 6.0 under stirring, and the solution added to a stirred suspension of 10.00 g (42.51 mmol) (RS)-1-(4-hydroxyphenyl)-5-oxo-pyrrolidine-3-carboxylic acid methyl ester (99.7%) in 40 mL methylcyclohexane. The mixture was heated to 28° C. and the pH readjusted to 6.0 with 2 M NaOH. The reaction was started by adding 33.2 mg Candida cylindraceae cholesterase (16.88 kU/g), and the pH was maintained at 6.0 by the controlled addition of 1.0 M NaOH solution under stirring. After a total consumption of 20.35 mL (20.35 mmol) 1.0 M sodium hydroxide solution (after 17.1 h; 47.9% conversion) the reaction mixture was passed through a sintered glass filter. The filtrate spontaneously separated into an aqueous and an organic phase.The aqueous phase was washed with 2×200 mL ethyl acetate to remove uncleaved ester. The aqueous phase was set to pH 4.0 with 25% sulfuric acid and concentrated in vacuo to a volume of ca. 80 mL (bath 60° C.). The solution was cooled to 1° C. (formation of white precipitate/crystals) and the pH set to 1.5 with 25% sulfuric acid. The precipitate/crystals were stirred overnight at 1° C., filtered off on a sintered glass filter (washed with a minimum amount of water) and dried overnight on high vacuum (RT, 6×10−2 mbar) to give 4.32 g (19.53 mmol; 45.9%) (S)-1-(4-hydroxyphenyl)-5-oxo-pyrrolidine-3-carboxylic acid. Analysis: HPLC (area A226nm): 99.3%, 0.7% ester. 98.9%ee. The product contains 5.3% water (according to Karl Fischer determination) and 2.1% (w/w) PEG (according to NMR).

Workup

  1. additionby adding 33.2 mg Candida cylindraceae cholesterase (16.88 kU/g)
  2. stirringunder stirring
  3. filtrationfilter
  4. customThe filtrate spontaneously separated into an aqueous and an organic phase.The aqueous phase
  5. washwas washed with 2×200 mL ethyl acetate
  6. customto remove uncleaved ester
  7. concentrationconcentrated in vacuo to a volume of ca. 80 mL (bath 60° C.)
  8. temperatureThe solution was cooled to 1° C. (formation of white precipitate/crystals)
  9. stirringThe precipitate/crystals were stirred overnight at 1° C.
  10. filtrationfiltered off on a sintered glass
  11. filtrationfilter (
  12. washwashed with a minimum amount of water) and
  13. customdried overnight on high vacuum (RT, 6×10−2 mbar)

Sources & evidence

ORD record
ord-a4c45e2ea78c405892bb3642a1dcea14
Source dataset
uspto-grants-2006_12
Patent number
US07148362B2

Reaction notes

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