L-Pyroglutamic Acid → Isopropyl 5-oxo-L-prolinate

HRID 17815

Reaction equation

HRID 17815 reaction equation
[NH:1]1[C:5](=[O:6])[CH2:4][CH2:3][C@H:2]1[C:7]([OH:9])=[O:8].O.[C:11]1(C)[CH:16]=CC(S(O)(=O)=O)=C[CH:12]=1>C(O)(C)C.CCOCC>[NH:1]1[C:5](=[O:6])[CH2:4][CH2:3][C@H:2]1[C:7]([O:9][CH:11]([CH3:16])[CH3:12])=[O:8]

Participants

5

Reactant 2

HCID 7405L-Pyroglutamic AcidHCID 521998p-Toluenesulfonic acid monohydrate

Product 1

HCID 14038124Isopropyl 5-oxo-L-prolinateYield 955.6%

Reagents, catalysts & solvents 2

HCID 3283Diethyl EtherSolventHCID 3776IsopropanolSolvent

Procedure

A solution of L-pyroglutamic acid (Aldrich, 25.0 g, 195 mmol) and para-toluenesulfonic acid mono hydrate (3.71 g, 19.5 mmol) was refluxed in isopropanol (40 mL) under nitrogen for 6 hours using a Dean-Stark trap variation (condensate returned through a Soxhlet extractor filled with 4 Å molecular sieves). After cooling to room temperature, the reaction was diluted with ether, washed with saturated aqueous sodium bicarbonate and then saturated aqueous NaCl, dried (MgSO4) and evaporated to give a colorless syrup. It crystallized upon setting. Triturating the crystalline residue in hexane provided 31.9 g (96%) of isopropyl pyrrolidin-5-one-2(S)-carboxylate as white prisms: 1H NMR (300 MHz, Chloroform-D) δ 6.35 (br s, 1 H), 5.04 (sept. 1H, J=6.2 Hz), 4.18 (dd, 1H, J=8.4, 5.3 Hz), 2.51-2.28 (m, 3H), 2.27-2.12 (m, 1H), 1.24 (d, 6H, J=6.2 Hz). LCMS m/z 172 (M+H)+.

Workup

  1. additionfilled with 4 Å molecular sieves)
  2. washwashed with saturated aqueous sodium bicarbonate
  3. dry with materialsaturated aqueous NaCl, dried (MgSO4)
  4. customevaporated
  5. customto give a colorless syrup
  6. customIt crystallized
  7. customTriturating the crystalline residue in hexane

Sources & evidence

ORD record
ord-362936ede8234b00bc667f0948035770
Source dataset
uspto-grants-2010_06
Patent number
US07741281B2

Linked notes

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