Methods for converting CBD, CBDA and analogs thereof into Δ8-THC, Δ8-THCA and analogs thereof

Patent metadata

Field	Value
Publication number	US-12398113-B2
Application number	US-202117644690-A
Country	US
Kind code	B2
Filing date	Dec 16, 2021
Priority date	Jun 11, 2019
Publication date	Aug 26, 2025
Grant date	Aug 26, 2025

Abstract

Disclosed herein are methods for converting cannabidiol, cannabidiolic acid and analogs thereof into Δ 8 -tetrahydrocannabinol, Δ 8 -tetrahydrocannabinolic acid and analogs thereof. In particular, there is provided a method for converting a compound of Formula (I) as defined herein into a compound of Formula (II) as defined herein, the method comprising heating the compound of Formula (I) and a Lewis acidic heterogeneous reagent in an aprotic-solvent system to provide a compound of Formula (II), wherein the Lewis-acidic heterogeneous reagent is acidic alumina.

First claim

The invention claimed is:

1. A method for converting a compound of Formula (I) into a compound of Formula (II), the method comprising heating a compound of Formula (I)

and a Lewis-acidic heterogeneous reagent in an aprotic-solvent system, to provide a compound of Formula (II)

wherein the Lewis-acidic heterogeneous reagent is acidic alumina, and
wherein:
R 1 is hydrogen or COOH, and
R 2 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.

2. The method of claim 1 , wherein the heating step occurs at a temperature in a range from about 80° C. to about 110° C.

3. The method of claim 1 , wherein the heating step occurs at a temperature in a range from about 80° C. to about 100° C.

4. The method of claim 1 , wherein the heating step occurs at a temperature in a range from about 80° C. to about 95° C.

5. The method of claim 1 , wherein the heating step occurs in an inert atmosphere.

6. The method of claim 1 , wherein the heating step is performed in a stirred tank reactor or a rotary bed reactor.

7. The method of claim 1 , wherein the Lewis-acidic heterogeneous reagent is in an amount of between about 0.1 to about 100 molar equivalents with respect to the compound of Formula (I).

8. The method of claim 1 , wherein the Lewis-acidic heterogeneous reagent is in an amount of between about 1 to about 50 molar equivalents with respect to the compound of Formula (I).

9. The method of claim 1 , wherein the Lewis-acidic heterogeneous reagent is in an amount of between about 1 to about 25 molar equivalents with respect to the compound of Formula (I).

10. The method of claim 1 , wherein the Lewis-acidic heterogeneous reagent is in an amount of between about 1 to about 10 molar equivalents with respect to the compound of Formula (I).

11. The method of claim 1 , wherein the Lewis-acidic heterogeneous reagent is in an amount of between about 1 to about 5 molar equivalents with respect to the compound of Formula (I).

12. The method of claim 1 , wherein the aprotic-solvent system comprises acetone, dimethyl sulfoxide, ethyl acetate, dichloromethane, chloroform, toluene, pentane, heptane, hexane, diethyl ether, tert-butyl methyl ether, tetrahydrofuran, dioxane, dimethylformamide, dimethylacetamide, N-methylpyrrolidone, anisole, butyl acetate, cumene, ethyl formate, isobutyl acetate, isopropyl acetate, methyl acetate, methylethylketone, methylisobutylketone, propyl acetate, cyclohexane, para-xylene, meta-xylene, ortho-xylene, or 1,2-dichloroethane, or any combination thereof.

13. The method of claim 1 , wherein the aprotic-solvent system is heptane.

14. The method of claim 1 , further comprising drying the acidic alumina before the heating step.

15. The method of claim 1 , wherein R 1 is hydrogen.

16. The method of claim 1 , wherein R 2 is C 3 H 7 , C 5 H 11 or C 7 H 15 .

17. The method of claim 1 , wherein the compound of Formula (I) is cannabidiol (CBD) and the compound of Formula (II) is Δ 8 -tetrahydrocannabinol (Δ 8 -THC).

18. A method for converting cannabidiol (CBD) into Δ 8 -tetrahydrocannabinol (Δ 8 -THC), the method comprising heating CBD and a Lewis-acidic heterogeneous reagent in an aprotic-solvent system at a temperature in a range from about 80° C. to about 110° C., and wherein the Lewis-acidic heterogeneous reagent is acidic alumina and is in an amount of between about 1 to about 100 molar equivalents with respect to CBD.

19. The method of claim 18 , wherein the aprotic-solvent system comprises acetone, dimethyl sulfoxide, ethyl acetate, dichloromethane, chloroform, toluene, pentane, heptane, hexane, diethyl ether, tert-butyl methyl ether, tetrahydrofuran, dioxane, dimethylformamide, dimethylacetamide, N-methylpyrrolidone, anisole, butyl acetate, cumene, ethyl formate, isobutyl acetate, isopropyl acetate, methyl acetate, methylethylketone, methylisobutylketone, propyl acetate, cyclohexane, para-xylene, meta-xylene, ortho-xylene, or 1,2-dichloroethane, or any combination thereof.

20. The method of claim 18 , wherein the aprotic-solvent system is heptane.

Assignees

• Canopy Growth Corp

Inventors

• Adair Christopher
• Gallant Roger
• Geiling Ben
• Haghdoost Manjili Mohammadmehdi

Classifications

• C07D311/80 Primary

  Dibenzopyrans; Hydrogenated dibenzopyrans · CPC title

• B01J29/40

  of the pentasil type, e.g. types ZSM-5, ZSM-8 or ZSM-11, as exemplified by patent documents US3702886, GB1334243 and US3709979, respectively · CPC title

• C07D311/78 Primary

  Ring systems having three or more relevant rings · CPC title