Morpholine → (S)-4-((5-Oxo-2-pyrrolidinyl)carbonyl)morpholine

HRID 1021022Notes

Reaction equation

HRID 1021022 reaction equation
CO[C:3](=[O:10])[C@@H:4]1[CH2:8][CH2:7][C:6](=[O:9])[NH:5]1.[NH:11]1[CH2:16][CH2:15][O:14][CH2:13][CH2:12]1>CN(C)C1C=CN=CC=1.C1(C)C=CC=CC=1>[N:11]1([C:3]([C@H:4]2[NH:5][C:6](=[O:9])[CH2:7][CH2:8]2)=[O:10])[CH2:16][CH2:15][O:14][CH2:13][CH2:12]1

Participants

5

Reactant 2

HCID 8083MorpholineHCID 78646Methyl 5-oxo-L-prolinate

Product 1

HCID 21117841(S)-4-((5-Oxo-2-pyrrolidinyl)carbonyl)morpholine

Reagents, catalysts & solvents 2

HCID 142844-(Dimethylamino)pyridineCatalystHCID 1140TolueneSolvent

Procedure

L-pyroglutamic acid methyl ester (23.91 g, 177 mmol), morpholine (21.8 g, 250 mmol) and 4-dimethylaminopyridine (0.2 g, 1.64 mmol) are heated under reflux in toluene (130 ml) for 12 hours. The product precipitates as an oil. The oil is separated from the toluene, diluted with dichloromethane (100 ml) and washed successively with 0.1 M HCl, 0.1 M NaOH and water (50 ml each). The dichloromethane phase is concentrated to obtain a suspension, which is filtered yielding the crude product. The crude product is dissolved in THF (200 ml) at 45° C. and, upon cooling in an ice bath, (S)-5-morpholine-4-carbonyl)pyrrolidin-2-one precipitates as white crystals. Enantiopurity (GC) 88.7% (S)-Enantiomer.

Workup

  1. customThe product precipitates as an oil
  2. customThe oil is separated from the toluene
  3. additiondiluted with dichloromethane (100 ml)
  4. washwashed successively with 0.1 M HCl, 0.1 M NaOH and water (50 ml each)
  5. concentrationThe dichloromethane phase is concentrated
  6. customto obtain a suspension, which
  7. filtrationis filtered

Sources & evidence

ORD record
ord-6fb0cfab1e3f41118620d894f3a4ad75
Source dataset
uspto-grants-2014_05
Patent number
US08716495B2

Reaction notes

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