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US 5,399,765 AGranted
Enantioselective preparation of optically pure albuterol
AssigneeSepracor Inc.
InventorsYun Gao, Charles M. Zepp
Life of this patent
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Abstract
The invention relates to a method for producing albuterol by the resolution of a mixture of enantiomers of 5-[2-[(1,1-dimethylethyl)amino]-1-hydroxyethyl]-2-hydroxybenzoate using ditoluoyltartaric acid.
Claims14
A method for obtaining a single enantiomer of methyl 5-[2-[(1,1-dimethylethyl)amino]-1-hydroxyethyl]-2-hydroxybenzoate comprising the steps of:
- (a) dissolving a mixture of enantiomers of methyl 5-[2-[(1,1-dimethylethyl)amino]-1-hydroxyethyl]-2-hydroxybenzoate and a chiral acid selected from the group consisting of (-)-di-toluoyl-L-tartaric acid and (+)-di-toluoyl-D-tartaric acid in methanol by heating to form a solution;
- (b) allowing said solution to cool, whereby a salt of primarily one stereoisomer crystallizes;
- (c) separating said salt from said solution;
- (d) recrystallizing said salt from methanol, whereby a diastereomeric salt having greater than 90% ee of an enantiomer of methyl 5-[2-[(1,1-dimethylethyl)amino]-1-hydroxyethyl]-2-hydroxybenzoate is obtained
- (e) separating said diastereomeric salt from the methanol solvent;
- and
- (f) liberating said enantiomer of methyl 5-[2-[(1,1-dimethylethyl)amino]-1-hydroxyethyl]-2-hydroxybenzoate from said diastereomeric salt by treatment with base.
4 more elements
A method for making optically pure albuterol comprising the steps of:
- (a) dissolving a mixture of enantiomers of methyl 5-[2-[(1,1-dimethylethyl)amino]-1-hydroxyethyl]-2-hydroxybenzoate and a chiral acid selected from the group consisting of (-)-di-toluoyl-L-tartaric acid and (+)-di-toluoyl-D-tartaric acid in methanol by heating to form a solution;
- (b) allowing said solution to cool, whereby a salt of primarily one stereoisomer crystallizes;
- (c) separating said salt from said solution;
- (d) recrystallizing said salt from methanol, whereby a diastereomeric salt having greater than 90% ee of an enantiomer of methyl 5-[2-[(1,1-dimethylethyl)amino]-1-hydroxyethyl]-2-hydroxybenzoate is obtained;
- (e) separating said diastereomeric salt from the methanol solvent;
- (f) liberating the enantiomer of methyl 5-[2-[(1,1-dimethylethyl)amino]-1-hydroxyethyl]-2-hydroxybenzoate from said diastereomeric salt by treatment with base;
- and
- (g) reducing said enantiomer of methyl 5-[2-[(1,1-dimethylethyl)amino]-1-hydroxyethyl]-2-hydroxybenzoate thereby forming optically active albuterol.
5 more elements
Dependencies are inferred from the claim text.