Synthesis of d-2-amino-1-butanol
AssigneeAmerican Cyanamid Company
InventorBalwant Singh
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Abstract
D-2-Amino-1-butanol, for the synthesis of ethambutol hydrochloride, d,d'-2,2'-(ethylenediimino)di-1-butanol dihydrochloride, is produced in high purity and good yields by the reaction of butene-1, a nitrile, preferably an excess of acetonitrile, and chlorine to form N-[1-(chloromethyl)propyl]acetimidoyl chloride which is hydrolyzed to dl-2-amino-1-butanol, which can be isolated as the hydrochloride, or free base, or a mixture, resolved with L(+)- tartaric acid and the d-2-amino-1-butanol reacted with ethylene dichloride and then hydrochloric acid to form ethambutol hydrochloride. A minimum of by-products which are conveniently split out permits the economical synthesis of a pharmaceutical grade product.
Claims14
A process for the isolation of d-2-amino-1-butanol from dl-2-amino-1-butanol containing up to about 10% of dl-1-amino-2-butanol which comprises forming a solution of said dl-2-amino-1-butanol containing dl-1-amino-2-butanol in anhydrous methanol, adding thereto L(+)-tartaric acid in at least about one-half molar quantity, and separating the crystalline acid L(+)-tartrate salt of d-2-amino-1-butanol from the methanol containing 1-2-amino-1-butanol and both d- and l- 1-amino-2-butanol.
In the production of dl-2-amino-1-butanol, or one of its optical isomers, as the free base, from the hydrochloride, the improvement comprising the process of adding an excess of NH.sub.3 to precipitate HCl as NH.sub.4 Cl, evaporating off excess NH.sub.3, and separating out the NH.sub.4 Cl, whereby there is neither excess NH.sub.3 or HCl remaining in the product free base of dl-amino-1-butanol, or one of its optical isomers.
In the production of dl-2-amino-1-butanol, or one of its optical isomers, as the free base, from the hydrochloride, the improvement comprising the process of adding an excess of NH.sub.3 to precipitate HCl as NH.sub.4 Cl, separating out the NH.sub.4 Cl, and evaporating off the excess NH.sub.3, whereby there is neither excess NH.sub.3 or HCl remaining in the product free base of dl-amino-1-butanol, or one of its optical isomers.
Dependencies are inferred from the claim text.