Methods of synthesizing cannabigerol, cannabigerolic acid, and analogs thereof

Patent metadata

Field	Value
Publication number	US-11795128-B2
Application number	US-202217883571-A
Country	US
Kind code	B2
Filing date	Aug 8, 2022
Priority date	May 12, 2020
Publication date	Oct 24, 2023
Grant date	Oct 24, 2023

Abstract

Disclosed are methods for preparing cannabigerol (CBG) or a CBG analog, embodiments of the method comprising providing a compound (I); combining the compound (I) with geraniol and a solvent to form a reaction mixture; and combining the reaction mixture with an acid catalyst to form a product mixture comprising the CBG or the CBG homolog. The method may further comprise separating the CBG or the CBG analog from the product mixture and may further comprise purifying the CBG or CBG analog. Methods for preparing cannabigerolic acid (CBGA) or a cannabigerolic acid analog are also disclosed. The present disclosure also provides highly purity CBG, CBGA, and analogs thereof.

First claim

The invention claimed is:

1. A method for preparing cannabigerolic acid (CBGA) or a CBGA analog, the method comprising:
reacting geraniol with a compound (I) of the following structure:

wherein R 1 is hydrogen, C 1 -C 12 alkyl, C 2 -C 12 alkenyl, C 2 -C 12 alkynyl, (OCH 2 CH 2 ) 0-6 O(C 1 -C 8 alkyl), (C 0 -C 4 alkyl)-NR 2a R 2b , (C 0 -C 4 alkyl)-aryl, (C 0 -C 4 alkyl)-heteroaryl, (C 0 -C 4 alkyl)-cycloalkyl, or (C 0 -C 4 alkyl)-heterocycloalkyl, wherein R 2a and R 2b are each independently hydrogen or C 1 -C 6 alkyl;
in the presence of an acid catalyst and optionally a solvent to form a cannabigerol (CBG) or a CBG analog, wherein the acid catalyst is acidic alumina, iron (III) perchlorate hydrate, or a combination thereof; and
reacting the CBG or CBG analog with methylmagnesium carbonate to provide the CBGA or CBGA analog.

2. The method of claim 1 , wherein the acid catalyst is acidic alumina.

3. The method of claim 1 , wherein the acid catalyst iron (III) perchlorate hydrate.

4. The method of claim 1 , wherein the compound (I) and geraniol are present in a compound (II):geraniol molar ratio of between 10:1 and 1:10.

5. The method of claim 1 , wherein R 1 is C 1 -C 12 alkyl.

6. The method of claim 1 , wherein R 1 is C 3 H 7 or C 7 H 15 .

7. The method of claim 1 , wherein R 1 is C 5 H 11 .

8. The method of claim 1 , wherein the solvent is present.

9. The method of claim 8 , wherein the solvent is chloroform, heptane, tert butylmethyl ether, diethyl ether, dichloromethane, dichloroethane, trifluorotoluene, hexane, cyclohexane, pentane, toluene, or any combination thereof.

10. A method for preparing cannabigerolic acid (CBGA) or a CBGA analog, the method comprising:
reacting geraniol with a compound (II) of the following structure:

wherein R 1 is hydrogen, C 1 -C 12 alkyl, C 2 -C 12 alkenyl, C 2 -C 12 alkynyl, (OCH 2 CH 2 ) 0-6 O(C 1 -C 8 alkyl), (C 0 -C 4 alkyl)-NR 2a R 2b (C 0 -C 4 alkyl)-aryl, (C 0 -C 4 alkyl)-heteroaryl, (C 0 -C 4 alkyl)-cycloalkyl, or (C 0 -C 4 alkyl)-heterocycloalkyl, wherein R 2a and R 2b are each independently hydrogen or C 1 -C 6 alkyl;
in the presence of an acid catalyst and optionally a solvent, wherein the acid catalyst is camphorsulfonic acid, acidic alumina, montmorillonite K10, iron (III) perchlorate hydrate, or a combination thereof; and
hydrolyzing with one or more mild hydrolysis reagents to provide the CBGA or CBGA analog.

11. The method of claim 10 , wherein the compound (II) and geraniol are present in a compound (II):geraniol molar ratio of between 10:1 and 1:10.

12. The method of claim 10 , wherein R 1 is C 1 -C 12 alkyl.

13. The method of claim 10 , wherein the reacting step is performed with heating.

14. The method of claim 10 , wherein the solvent is present.

15. The method of claim 14 , wherein the solvent is chloroform, heptane, tert butylmethyl ether, diethyl ether, dichloromethane, dichloroethane, trifluorotoluene, hexane, cyclohexane, pentane, toluene, or any combination thereof.

16. A method for preparing cannabigerolic acid (CBGA) or a CBGA analog, the method comprising:
reacting geraniol with a compound (II) of the following structure:

wherein R 1 is hydrogen, C 1 -C 12 alkyl, C 2 -C 12 alkenyl, C 2 -C 12 alkynyl, (OCH 2 CH 2 ) 0-6 O(C 1 -C 8 alkyl), (C 0 -C 4 alkyl)-NR 2a R 2b , (C 0 -C 4 alkyl)-aryl, (C 0 -C 4 alkyl)-heteroaryl, (C 0 -C 4 alkyl)-cycloalkyl, or (C 0 -C 4 alkyl)-heterocycloalkyl, wherein R 2a and R 2b are each independently hydrogen or C 1 -C 6 alkyl;
in the presence of acidic alumina and a solvent, wherein the compound (II) and geraniol are present in a compound (II):geraniol molar ratio of between 10:1 and 1:10; and
hydrolyzing with one or more mild hydrolysis reagents to provide the CBGA or CBGA analog.

17. The method of claim 16 , wherein the reacting step is performed with heating.

18. The method of claim 16 , wherein the solvent is chloroform, heptane, tert butylmethyl ether, diethyl ether, dichloromethane, dichloroethane, trifluorotoluene, hexane, cyclohexane, pentane, toluene, or any combination thereof.

19. The method of claim 16 , wherein R 1 is C 1 -C 12 alkyl.

Assignees

• Canopy Growth Corp

Inventors

• Brumar Daniel
• Fard Mahmood Azizpour
• Geiling Ben
• Haghdoost Manjili Mohammadmehdi

Classifications

• C07C37/16 Primary

  by condensation involving hydroxy groups of phenols or alcohols or the ether or mineral ester group derived therefrom · CPC title

• B01J21/04

  Alumina · CPC title

• B01J21/16

  Clays or other mineral silicates · CPC title

• B01J27/128

  with iron group metals or platinum group metals · CPC title

• B01J31/0229

  also containing elements or functional groups covered by B01J31/0201 - B01J31/0214 · CPC title