Acetic Anhydride → 5-Amino-5-oxopentanoic acid

HRID 2374701Notes

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

Reactant 3

HCID 7918Acetic Anhydride

HCID 14923Ammonium Hydroxide

HCID 10976240Isobutylglutaric acid

Product 1

HCID 1683565-Amino-5-oxopentanoic acid

Procedure

Accordingly, 3-isobutylglutaric acid, compound 1, is converted into the corresponding anhydride, compound 2, by treatment with acetic anhydride. The reaction of the anhydride with NH4OH produces the glutaric acid mono-amide, compound 3, which is resolved with (R)-1-phenylethylamine, yielding the (R)-phenylethylamine salt of (R)-3-(carbamoylmethyl)-5-methylhexanoic acid, compound 3-salt. Combining the salt with an acid liberates the R enantiomer, compound 4. Finally, Hoffmann degradation with Br2/NaOH provides (S)-Pregabalin.

Sources & evidence

ORD record: ord-e374d17cc5a844e3bba2eaa2e608d96b
Source dataset: uspto-grants-2008_12
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07462737B2

Reaction notes

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