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

HRID 1534533Notes

Reaction equation

HRID 1534533 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)CC1CO1)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 9898830Ethyl 2-(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-bb2540ea449e44d6b3b309e20ac1b1c6
Source dataset
uspto-grants-1992_02
Patent number
US05089518

Reaction notes

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