Regiospecific processes to make cis-1-amino-2-alkanol from diol
AssigneeMerck & Co., Inc.
InventorsThomas R. Verhoeven, F. Edward Roberts, Chris H. Senanayake, Kenneth M. Ryan
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Abstract
A regioselective processes are disclosed for the synthesis of (1R,1S)-amino-(2S,2R)-alkanol, particularly (1R,1S)-amino-(2S,2R)-indanol.
Claims6
A regioselective process for synthesizing any enantiomer of cis-1-amino-2-indanol, or mixture of said enantiomers, from 1,2-indane diol, said process substantially retaining the stereochemical integrity of the carbon-oxygen bond at C-2 in the 1,2-indane diol, wherein the process comprises the steps of
- (a) mixing one equivalent of 1,2-indane diol in a solvent, said solvent selected from an alkyl nitrile or aryl nitrile;
- (b) adding to the mixture at least about 1.5 equivalents of an acid, said acid selected from a strong protic acid or a Lewis acid or an organic acid, and maintaining thereafter the temperature of the resulting mixture between about -70.degree. C. and about 30.degree. C. for a time period of between about 0.25 hours to about 6.0 hours;
- and
- (c) adding excess water to effect hydrolysis, and stirring for a time period of between about 0.5 hour and about 8.0 hours, at a temperature of between about 25.degree. C. and about 80.degree. C., to give substantially cis-1-amino-2-indanol.
A regioselective process for synthesizing any enantiomer of cis-1-amino-2-indanol, or mixture of said enantiomers, from 1,2-indane diol, said process substantially retaining the stereochemical integrity of the carbon-oxygen bond at C-2 in the 1,2-indane diol, wherein the process comprises the steps of
- (a) mixing one equivalent of reactant 1,2-indane diol in acetonitrile;
- (b) adding dropwise to the mixture about two equivalents of concentrated sulfuric acid, and maintaining thereafter the temperature at about -70.degree.-30.degree. C. for about 30 minutes to one hour;
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- (c) adding excess water to effect hydrolysis, and stirring, at a temperature between about 25.degree. C. and about 80.degree. C., until hydrolysis is complete, to give substantially cis-1-amino-2-indanol.
Dependencies are inferred from the claim text.