Reaction equation
[CH2:1]([CH:3]([N:7]1[CH2:11][CH2:10][CH2:9][C:8]1=[O:12])[C:4]([OH:6])=[O:5])[CH3:2].N.NC(CC)C(N)=O>>[CH2:1]([CH:3]([N:7]1[CH2:11][CH2:10][CH2:9][C:8]1=[O:12])[C:4]([OH:6])=[O:5])[CH3:2].[CH2:1]([C@@H:3]([N:7]1[CH2:11][CH2:10][CH2:9][C:8]1=[O:12])[C:4]([OH:6])=[O:5])[CH3:2]Participants
Procedure
The enantioselective synthesis of both the (S)— and (R) enantiomers of 1 were disclosed in the U.S. Pat. No. 4,696,942 and U.S. Pat. No. 4,696,943 by the following processes respectively: a) optical resolution of alpha-ethyl-2-oxo-1-pyrrolidineacetic acid, activation of the chiral alpha-ethyl-2-oxo-1-pyrrolidineacetic acid with an alkylhaloformate and subsequent reaction with ammonia; b) cyclizing the chiral S or R amino-butanamide. In the former process, although optical resolution of racemic alpha-ethyl-2-oxo-1-pyrrolidineacetic acid gave (S) or (R)-alpha-ethyl-2-oxo-1-pyrrolidineacetic acid with satisfactory optical purity, this resolution provides less than 50% yield of the desired enantiomer, with the remaining (more than 50%) isomer mixture being discarded as a waste. Also, the amide formation step has to be performed at a very low temperature, normally between −30 to −40° C. to prevent epimerization, which is not convenient for large scale preparation. The latter process presents a drawback with the fact that the required enantiomeric precursors, (S)— and (R)-4-[[1-aminocarbonyl)propyl]amino]butyrate or (S)— and (R)—N-[1-(aminocarbonyl)propyl]4-halobutanamide, for the cyclization are not readily available.
Sources & evidence
- ORD record
- ord-d9fb132458d04bc5a9e9d4a8b491d7d0
- Source dataset
- uspto-grants-2011_03
- Patent number
- US07902380B2
Linked notes
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