p-Toluenesulfonic acid → 5-Benzyloxycarbonylamino-2-pyrrolidone

HRID 446125Notes

Reaction equation

[CH2:1]1[CH:6]2[NH:7][C:8](C[N:5]2[C:3](=[O:4])[CH2:2]1)=[O:9].C(OC1NC(=O)CC1)C.C(=O)([O:22][CH2:23][C:24]1[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=1)N.C1(C)C=CC(S(O)(=O)=O)=CC=1>>[CH2:23]([O:22][C:8]([NH:7][CH:6]1[NH:5][C:3](=[O:4])[CH2:2][CH2:1]1)=[O:9])[C:24]1[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=1

Participants

Reactant 4

HCID 6101p-Toluenesulfonic acid

HCID 12136Benzyl carbamate

HCID 65955Dimiracetam

HCID 35805555-Ethoxy-2-pyrrolidinone

Product 1

HCID 126384645-Benzyloxycarbonylamino-2-pyrrolidone

Procedure

WO 93/09120 describes a process for the preparation of dimiracetam (2,5-dioxohexa-hydro-1H-pyrrolo[1,2-a]imidazole) 1 and related compounds. 5-Ethoxy-2-pyrrolidone is reacted with benzyl carbamate with a catalytic amount of p-toluenesulfonic acid to give 5-benzyloxycarbonylamino-2-pyrrolidone. This compound is then deprotonated at the pyrrolidine nitrogen with sodium hydride in acetonitrile, and reacted with ethyl bromoacetate to give ethyl 5-benzyloxycarbonylamino-2-oxo-1-pyrrolidine-acetate 2. Cyclization can then be performed after cleavage of the ethyl ester and/or the benzyloxycarbonyl protecting group in the presence of a variety of cyclizing agents.

Sources & evidence

ORD record: ord-ed76dc5ab1f74346af6ad0f2e20990b3
Source dataset: uspto-grants-2013_07
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08476453B2

Reaction notes

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