L-Malic Acid → (S)-4-hydroxy-1-(2-propynyl)-2-pyrrolidinone

HRID 2107966Notes

Reaction equation

HRID 2107966 reaction equation
CO[C:3](=[O:19])[CH2:4][C@H:5]([OH:18])[CH2:6]OS(C1C=CC(C)=CC=1)(=O)=O.C(OC(=O)C[C@H](O)CI)C.C(OC(=O)C[C@H]1CO1)C.C(O)(=O)[C@H](CC(O)=O)O.[CH2:48]([NH2:51])[C:49]#[CH:50]>>[OH:18][C@@H:5]1[CH2:6][N:51]([CH2:48][C:49]#[CH:50])[C:3](=[O:19])[CH2:4]1

Participants

6

Reactant 5

HCID 222656L-Malic AcidHCID 239041PropargylamineHCID 10920539ethyl 2-[(2S)-oxiran-2-yl]acetateHCID 11140757(S)-3-hydroxy-4-[[(4-methylphenyl)sulfonyl]oxy]butanoic acid methyl ester2×HCID 13778740ethyl (3S)-3-hydroxy-4-iodobutanoate

Product 1

HCID 15046658(S)-4-hydroxy-1-(2-propynyl)-2-pyrrolidinone

Procedure

In accordance with Scheme I, (S)-3-hydroxy-4-[[(4-methylphenyl)sulfonyl]oxy]butanoic acid methyl ester 2, (S)-3-hydroxy-4-iodobutanoic acid ethyl ester 3 and (S)-oxiraneacetic acid ethyl ester 4 are prepared from (S)-malic acid 1 using previously described methods [S. Saito et. al. Chem. Lett. 1389, (1984) and M. Larcheveque et. al. Tetrahedron Lett. 1781, 28 (1987)]. The esters 2, 3 and 4 are individually reacted with propargylamine in an alcohol solvent at temperatures ranging from room temperature to the reflux temperature of the solvent, preferably in the presence of an alkali metal carbonate, to produce (S)-4-hydroxy-1-(2-propynyl)-2-pyrrolidinone 5. Compound 5 is then reacted with an aryl or a (C1 -C6) carboxylic acid anhydride such as acetic anhydride in the presence of pyridine and preferably dimethylaminopyridine in an ether or a chlorohydrocarbon solvent, such as dichloromethane, to give the intermediate of general formula 6, for example, (S)-4-(acetyloxy)-1-(2-propynyl)-2 -pyrrolidinone.

Sources & evidence

ORD record
ord-5c89e09a74d04a039af15e6d94235706
Source dataset
uspto-grants-1990_06
Patent number
US04937235

Reaction notes

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