4-cyano-3-hydroxybutanoyl hydrazines, derivatives and process for the preparation thereof
AssigneeBoard of Trustees operating Michigan State University
InventorsRawle I. Hollingsworth, Guijun Wang
Life of this patent
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Abstract
Novel 4-cyano-3-hydroxybutanoyl hydrazides (10), particularly R-chiral intermediates are described. The intermediates are useful in preparing (R)-3-hydroxy-4-trimethylaminobutyric acid (L-carnitine) and R-4-amino-3-hydroxybutyric acid (GABOB) and chiral chemical intermediates which are medically useful.
Claims9
4-Cyano-3-hydroxybutanoyl hydrazide.
R-4-Cyano-3-hydroxybutanoyl hydrazide.
A process for the preparation of 4-cyano-3-hydroxybutanoyl hydrazide which comprises:
- (a) reacting 4-cyano-3-hydroxybutyric acid alkyl ester, where alkyl contains 1 to 6 carbon atoms, with anhydrous hydrazine in a polar organic solvent to produce the 4-cyano-3-hydroxybutanoyl hydrazide in a reaction mixture;
- and
- (b) separating the 4-cyano-3-hydroxylbutanoyl hydrazide from the reaction mixture to produce the 4-cyano-3-hydroxybutanoyl hydrazide.
A process for the preparation of 3-cyano-3-hydroxybutanoyl hydrazide which comprises:
- (a) reacting 4-cyano-3-hydroxybutyric acid alkyl ester, where alkyl contains 1 to 6 carbon atoms, with anhydrous hydrazine in absolute ethanol in the absence of water to produce the 4-cyano-3-hydroxybutanoyl hydrazide in a reaction mixture as a precipitate;
- and
- (b) separating the precipitate from the reaction mixture to produce the 4-cyano-3-hydroxybutanoyl hydrazide.
A process for the preparation of 4-amino-3-hydroxybutyronitrile which comprises:
- (a) reacting 4-cyano-3-hydroxy butyric acid alkyl ester, where alkyl contains 1 to 6 carbon atoms, with anhydrous hydrazine in a polar organic solvent to produce 4-cyano-3-hydroxybutanoyl hydrazide in a reaction mixture:
- (b) separating the 4-cyano-3-hydroxybutanoyl hydrazide from the reaction mixture to produce the 4-cyano -3-hydroxybutanoyl hydrazide;
- and
- (c) reacting 4-cyano-3-hydroxybutanoyl hydrazide with a decarboxylation and rearrangement agent to produce the 4-amino-3-hydroxybutyronitrile as a salt in a reaction mixture;
- and
- (d) separating the 4-amino-3-hydroxybutyronitrile as a salt from the reaction mixture.
A process for the preparation of 4-amino-3-hydroxybutyronitrile which comprises:
- (a) reacting 4-cyano-3-hydroxy butyric acid alkyl ester, where alkyl contains 1 to 6 carbon atoms, with anhydrous hydrazine in absolute ethanol in the absence of water to produce 4-cyano-3-hydroxybutanoyl hydrazide in a reaction mixture as a precipitate;
- (b) separating the precipitate from the reaction mixture to produce the 4-cyano-3-hydroxybutanoyl hydrazide;
- and
- (c) reacting 4-cyano-3-hydroxybutanoyl hydrazide with nitrous acid to produce the 4-amino-3-hydroxybutyronitrile as a salt in a reaction mixture;
- and
- (d) separating the 4-amino-3-hydroxybutyronitrile as a salt from the reaction mixture.
Dependencies are inferred from the claim text.