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

HRID 1500409Notes

Reaction equation

HRID 1500409 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-02324d36dbc3418ca586b433001f9f34
Source dataset
uspto-grants-2015_12
Patent number
US09206116B2

Reaction notes

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