Stereochemically defined polypropionates and methods for making and using the same

Patent metadata

Field	Value
Publication number	US-10160768-B2
Application number	US-201515501658-A
Country	US
Kind code	B2
Filing date	Aug 4, 2015
Priority date	Aug 4, 2014
Publication date	Dec 25, 2018
Grant date	Dec 25, 2018

Abstract

The present invention relates to stereochemically defined polypropionates and methods for preparing and using the same. The stereochemically defined polypropionates may be useful in the synthesis of natural products and/or natural product-like libraries.

First claim

We claim:

1. A process for preparing a compound of Formula 1:

comprising the steps of:
reacting 6,8-dimethyl-3,9-dioxatricyclo[3.3.1.0 2,4 ]nonan-7-one with a reducing agent to form an intermediate having the following structure:

and
reacting the intermediate with an acid to form the compound of Formula 1.

2. A process for resolving enantiomers of a compound of Formula 1:

comprising the steps of:
reacting the racemic compound of Formula 1 with phthalic anhydride to form a racemic mixture of phthalates of Formulas 2A and 2B having the structure:

reacting the racemic mixture of phthalates of Formulas 2A and 2B with a first chiral amine in a solvent to form a pair of diastereomeric salts thereof in a solution;
precipitating a first diastereomeric salt of the pair of diastereomeric salts from the solution to provide an isolated first diastereomeric salt and an second diastereomeric salt; and
forming the enantiomers of the compound of Formula 1 from the isolated first diastereomeric salt and the second diastereomeric salt, thereby resolving the enantiomers of the compound of Formula 1″.

3. The process of claim 2 , wherein the isolated first diastereomeric salt is treated with a base to form a first enantiomeric compound of Formula 1.

4. The process of claim 3 , wherein the first enantiomeric compound of Formula 1 is the compound of Formula 1B:

or a salt thereof.

5. The process of claim 2 , further comprising the steps of:
acidifying the second diastereomeric salt to form a free phthalate;
reacting the free phthalate with a second chiral amine to reform the second diastereomeric salt in a solution;
precipitating the second diastereomeric salt from the solution to form an isolated second diastereomeric salt; and

forming a second enantiomeric compound of Formula 1 from the isolated second diastereomeric salt.

6. The process of claim 5 , wherein the second enantiomeric compound of Formula 1 is the compound of Formula 1A

Assignees

• Eisai R&D Man Co Ltd

Inventors

• Fang Francis G
• Choi Hyeong-Wook
• Campagna Silvio
• Mathieu Steven

Classifications

• C07D493/22 Primary

  in which the condensed system contains four or more hetero rings · CPC title

• C07D493/18

  Bridged systems · CPC title

• C07D313/00

  Heterocyclic compounds containing rings of more than six members having one oxygen atom as the only ring hetero atom · CPC title

• C07D493/08

  Bridged systems · CPC title

• C07B57/00

  Separation of optically-active compounds · CPC title