Acetic Anhydride → 5-Amino-5-oxopentanoic acid

反応式

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]

参加物

反応物 3

HCID 7918Acetic Anhydride

HCID 14923Ammonium Hydroxide

HCID 10976240Isobutylglutaric acid

生成物 1

HCID 1683565-Amino-5-oxopentanoic acid

実験手順

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.

出典と根拠

ORDレコード: ord-e0863cdf1202435d983cdcce1d8c1fc1
出典データセット: uspto-grants-2008_11
DOI: 10.6084/m9.figshare.5104873.v1
特許番号: US07446220B2

反応ノート

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