Morpholine → 4-((5-Oxo-2-pyrrolidinyl)carbonyl)morpholine
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>C1(C)C(C)=CC=CC=1>[N:11]1([C:3]([CH: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]1Participants
Reactant 2
Product 1
Reagents, catalysts & solvents 1
Conditions
- Temperature
- 140 °C
Procedure
A mixture of 143 g of pyroglutamic acid methyl ester (1 mol) and 139 g morpholine (1.60 mol) in 900 ml of xylene is heated to 140° C. for 20 h. The xylene is evaporated to a volume of 500 ml. From the suspension obtained, the precipitate is filtered off, washed with THF to yield the desired compound after drying in vacuo. From the filtrate the solvent is evaporated completely. This crude product [(R/S)-5-(morpholine-4-carbonyl)pyrrolidin-2-one] is filtered over 800 g silica gel with THF as the solvent and evaporated to dryness to yield a second crop of the desired compound. This compound is used directly in the next step. HPLC analysis shows the material to be in an enantiomeric ratio: 55.8:44.2 [(4-a, R1=H; R4=morpholine): (4-b, R1=H; R4=morpholine), respectively].
Workup
- customThe xylene is evaporated to a volume of 500 ml
- customFrom the suspension obtained
- filtrationthe precipitate is filtered off
- washwashed with THF
Sources & evidence
- ORD record
- ord-61fd4471621b4c6fb43a1aacaeb7692b
- Source dataset
- uspto-grants-2014_05
- Patent number
- US08716495B2
Reaction notes
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