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

HRID 1641628Notes

Reaction equation

HRID 1641628 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-6fc290d6101b46ce8bcc643c7a4c1a12
Source dataset
uspto-grants-2012_02
Patent number
US08115016B2

Reaction notes

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