Acetic Anhydride → 5-Amino-5-oxopentanoic acid
Reaction equation
C([CH:5]([CH2:10][C:11]([OH:13])=[O:12])[CH2:6][C:7](O)=[O:8])C(C)C.C(OC(=O)C)(=O)C.[NH4+:21].[OH-]>>[C:7]([NH2:21])(=[O:8])[CH2:6][CH2:5][CH2:10][C:11]([OH:13])=[O:12]Participants
4
Procedure
In Scheme 1, 3-isobutyl glutaric 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)-phenylethylamine 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 degradation with Br2/NaOH provides (S)-Pregabalin. A disadvantage of this method is that it requires separating the two enantiomers, thereby resulting in the loss of half the product, such that the process cost is high.
Sources & evidence
- ORD record
- ord-18280e068cbf4b29b32532f3cb590136
- Source dataset
- uspto-grants-2012_07
- Patent number
- US08212071B2
Reaction notes
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