Methods of synthesizing cannabigergol, cannabigerolic acid, and analogs thereof

Patent metadata

Field	Value
Publication number	US-11384040-B2
Application number	US-202117495058-A
Country	US
Kind code	B2
Filing date	Oct 6, 2021
Priority date	May 12, 2020
Publication date	Jul 12, 2022
Grant date	Jul 12, 2022

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 cannabigerol (CBG) analog, comprising:
reacting geraniol with a compound (I) of the following structure:

wherein R 1 is hydrogen, C 1 -C 4 alkyl, C 6 -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 optionally a solvent.

2. The method of claim 1 , wherein the method includes the solvent.

3. The method of claim 2 , wherein the solvent is chloroform, heptane, tert-butylmethyl ether, diethyl ether, dichloromethane, dichloroethane, trifluorotoluene, hexane, cyclohexane, pentane, toluene, or any combination thereof.

4. The method of claim 1 , wherein the compound (I) and geraniol are present in a compound (I):geraniol molar ratio of between about 1:1.5 and about 1:3.5.

5. The method of claim 1 , wherein R 1 is C 1 -C 4 alkyl, C 6 -C 12 alkyl.

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

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

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

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

10. The method of claim 1 , wherein the acid alumina is in an amount of between about 0.001 and about 10 molar equivalents with respect to the compound (I).

11. The method of claim 1 , wherein the acid alumina is in an amount of between about 0.001 and about 1 molar equivalents with respect to the compound (I).

12. The method of claim 1 , wherein the reacting step is performed with heating.

13. A method for preparing a cannabigerol (CBG) analog, comprising:
reacting geraniol with a compound (I) of the following structure:

wherein R 1 is C 1 -C 4 alkyl, C 6 -C 12 alkyl;
in the presence of acidic alumina an acid catalyst and a solvent.

14. The method of claim 13 , wherein the solvent is chloroform, heptane, tert-butylmethyl ether, diethyl ether, dichloromethane, dichloroethane, trifluorotoluene, hexane, cyclohexane, pentane, toluene, or any combination thereof.

15. The method of claim 13 , wherein the compound (I) and geraniol are present in a compound (I):geraniol molar ratio of between about 10:1 and about 1:10.

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

17. A method for preparing cannabigerol (CBG) or a CBG analog, 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;
under heating in the presence of acidic alumina and a solvent,
wherein the compound (I) and geraniol are present in a compound (I):geraniol molar ratio of between about 10:1 and about 1:10.

18. The method of claim 17 , 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 17 , 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

• B01J21/16

  Clays or other mineral silicates · CPC title

• C07C51/00

  Preparation of carboxylic acids or their salts, halides or anhydrides (of acids by hydrolysis of oils, fats or waxes C11C) · CPC title

• B01J27/128

  with iron group metals or platinum group metals · CPC title

• B01J31/0225

  comprising sulfonic acid groups or the corresponding salts · CPC title