Process of making adamantanamides

Patent metadata

Field	Value
Publication number	US-9840466-B2
Application number	US-201415038754-A
Country	US
Kind code	B2
Filing date	Dec 4, 2014
Priority date	Dec 9, 2013
Publication date	Dec 12, 2017
Grant date	Dec 12, 2017

Abstract

An effective process of making adamantanamide, which process is fast, does not the use of organic solvents or labor-intensive isolation or purification of the product, by removal of organic solvent or by-products, and has improved yield and purity.

First claim

The invention claimed is:

1. A process of making an adamantanamide, the process comprising the steps:
i. mixing 0.9 to 1 molar equivalents of an alkylamine and 1.0-1.5 molar equivalents of a base in sufficient water to obtain a concentration of the alkylamine in the aqueous solution between 0.1 to 1.0 M and the pH between 8 to 14;
ii. heating the mixture to a temperature in the range of from 50° C. to 90° C., to obtain a heated aqueous basic solution of the alkylamine;
iii. adding 1 molar equivalent of adamantanecarbonyl chloride to the heated aqueous basic solution of alkylamine, to obtain a bi-phasic mixture;
iv. stirring the bi-phasic mixture of the alkylamine and the adamantanecarbonyl chloride and maintaining the temperature in the range of from 50° C. to 90° C., until the reaction is completed;
v. stirring and allowing the reaction mixture to cool to below 30° C., to precipitate the adamantanamide product out of the reaction mixture; and
vi. separating the adamantanamide product from the reaction mixture.

2. The process according to claim 1 , wherein the process further comprises an additional step, wherein residual adamantanecarboxylic acid salt in the reaction mixture is recycled and converted to adamantanecarbonyl chloride.

3. The process according to claim 1 or claim 2 wherein the base is an inorganic base.

4. The process according to claim 3 wherein the base selected from the group consisting of alkali metal hydroxides, carbonates, and mixtures thereof.

5. The process according to claim 3 wherein the base is sodium hydroxide.

6. The process according to any one of claims 1 to 5 wherein, wherein the temperature is in the range of from 55° C. to 80° C.

7. The process according to any one of claims 1 to 6 wherein the pH in step (i) is in the range of from 10 to 12.

8. The process according to any one of claims 1 to 7 wherein the reaction completion takes from 15 minutes to 2 hours.

9. The process of any one of claims 1 to 8 wherein adamantanecarbonyl chloride added in step (iii) has been pre-melted.

10. The process of any one of claims 1 to 8 wherein adamantanecarbonyl chloride added in step (iii) is added gradually, as a solid.

Assignees

• Conopco Inc

Inventors

• Harichian Bijan
• Rosa Jose Guillermo

Classifications

• C07D217/06

  with the ring nitrogen atom acylated by carboxylic or carbonic acids, or with sulfur or nitrogen analogues thereof, e.g. carbamates · CPC title

• C07D211/62

  attached in position 4 · CPC title

• C07D211/16 Primary

  with acylated ring nitrogen atom · CPC title

• C07C2603/74

  Adamantanes · CPC title

• C07C231/02

  from carboxylic acids or from esters, anhydrides, or halides thereof by reaction with ammonia or amines · CPC title