Process for preparing pure enantiomers of tropic acid esters

• US 5,952,505 A
• Filed: 11/19/1997
• Issued: 09/14/1999
• Est. Priority Date: 04/28/1995
• Status: Expired due to Term

• Current Assignee: Boehringer Ingelheim Promeco SA de CV (C.H. Boehringer Sohn AG & Co. KG)
• Original Assignee: Boehringer Ingelheim Promeco SA de CV (C.H. Boehringer Sohn AG & Co. KG)
• Inventors: Banholzer, Rolf
• Primary Examiner(s): Rotman, Alan L.
• Application Number:
  US08/945,142
• Time in Patent Office: 664 Days
• Field of Search: 546/127, 546/112
• US Class Current: 546/127
• CPC Class Codes: C07D 451/10 acylated by aliphatic or araliphatic carboxylic acids, e.g. atropine, scopolamine

Abstract

Precursors of anticholinergically active quaternary compounds can be synthesized from optically active tropic acid by acetylation, conversion into the acid chloride, reaction with amino alcohols of formula (I) ##STR1## (as the methanesulphonate; Q and R are explained in the specification), deacetylation and isolation of the reaction product.

Claims

1. A process for preparing enantiomerically pure (+)-tropic acid esters of an amino alcohol of Formula (I) ##STR4## wherein Q is CH₂ --CH₂, CH₂ --CH₂ --CH₂, ##STR5## and R is a straight-chained or branched C_1-4 -alkyl group

which comprises the steps of

(a) acetylating a tropic acid of Formula A ##STR6## with acetychloride to form acetylated tropic acid of Formula (B) ##STR7## (b) converting for acetylated tropic acid (B) into acetylated tropic acid chloride of Formula (C). ##STR8## with thionyl chloride;

(c) reacting the acetylated tropic acid chloride (C) at ambient temperature in an inert solvent with the methanesulphonate of the amino alcohol of Formula (I) in the presence of an excess of aluminum oxide to form a tropic acid ester of Formula (D) ##STR9## (d) deacetylating the tropic acid ester (D) in the presence of about 2 to about 20% hydrochloric acid to form deacetylated tropic acid ester of Formula (E) ##STR10## (e) isolating the deacetylated tropic acid ester (E) as a free base by treating with an excess of an aqueous sodium hydroxide or an alkali carbonate solution at a temperature of about -15°

C. to about 50°

C.

2. The process recited in claim 1 wherein N-isopropylnortropine is the amino alcohol of Formula (I).

3. A process for preparing enantiomerically pure (-)-tropic acid esters of an amino alcohol of Formula (I) ##STR11## wherein Q is CH₂ --CH₂, CH₂ --CH₂ --CH₂, ##STR12## and R is a straight-chained or branched C_1-4 -alkyl group which comprises the steps of

(a) acetylating a tropic acid of Formula (A'"'"') ##STR13## with acetychloride to form an acetylated tropic acid of Formula (B'"'"') ##STR14## (b) converting the acetylated tropic acid (B) into acetylated tropic acid chloride of Formula (C'"'"') ##STR15## with thionyl chloride;

(c) reacting the acetylated tropic acid chloride (c) at ambient temperature in an inert solvent with the methanesulphonate of the amino alcohol of Formula (I) in the presence of an excess of aluminum oxide to form a tropic acid ester of Formula (D'"'"') ##STR16## (d) deacetylating the tropic acid ester (D'"'"') in the presence of about 2 to about 20% hydrochloric acid to form deacetylated tropic acid ester of Formula (E'"'"') ##STR17## (e) isolating the deacetylated tropic acid ester (E'"'"') as a free base by treating with an excess of an aqueous sodium hydroxide or an alkali carbonate solution at a temperature of about -15°

C. to about 50°

C.

4. The process as recited in claim 3 wherein N-isopropylnotropine is the amino alcohol of Formula (I).