Acetic Anhydride → 5-Amino-5-oxopentanoic acid
Reaction equation
CC(C[C@H](C[NH2:11])CC(O)=O)C.C([CH:16]([CH2:21][C:22]([OH:24])=[O:23])[CH2:17][C:18](O)=[O:19])C(C)C.C(OC(=O)C)(=O)C.[NH4+].[OH-]>>[C:18]([NH2:11])(=[O:19])[CH2:17][CH2:16][CH2:21][C:22]([OH:24])=[O:23]Participants
Procedure
Several processes were reported for the synthesis of (S)-Pregabalin. One such process is illustrated in drugs of the future, 24 (8), 862-870 (1999), represented as scheme-1. In which 3-isobutylglutaric acid, compound 2, is converted into the corresponding anhydride, compound 3, by treatment with refluxing acetic anhydride. The reaction of the anhydride with NH4OH produces the glutaric acid mono-amide, compound 4, which is resolved with (R)-1-phenylethylamine, yielding the (R)-phenyl ethylamine salt of (R)-3-(carbamoylmethyl)-5-methylhexanoic acid, compound 5. Combining the salt with an acid liberates the (R)-enantiomer, compound 6. Finally, a Hoffmann's degradation with Br2/NaOH provides (S)-Pregabalin. A disadvantage of this method is that, it requires separating the two enantiomer thereby resulting in the loss of half of the product, such that the process cost is high.
Sources & evidence
- ORD record
- ord-3705a3b389014c03a826b041e0da8f3b
- Source dataset
- uspto-grants-2012_05
- Patent number
- US08168828B2
Reaction notes
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