SYNTHESIS OF CANNABINOIDS

• US 20190023680A1
• Filed: 06/29/2018
• Published: 01/24/2019
• Est. Priority Date: 07/21/2017
• Status: Active Grant

• Current Assignee: University of South Florida (State University System of Florida)
• Original Assignee: University of South Florida (State University System of Florida)
• Inventors: Leahy, James William, Shultz, Zachary Paul, Lawrence, Grant Alexander
• Granted Patent: US 10,640,482 B2
• Time in Patent Office: Days
• CPC Class Codes: C07B 2200/07 Optical isomers
• CPC Class Codes: C07C 2601/16 the ring being unsaturated
• CPC Class Codes: C07C 29/132 by reduction of an oxygen containing functional group
• CPC Class Codes: C07C 29/143 of ketones
• CPC Class Codes: C07C 37/055 the substituted group being bound to oxygen, e.g. ether group
• CPC Class Codes: C07C 39/23 polycyclic, containing six-membered aromatic rings and other rings, with unsaturation outside the aromatic rings
• CPC Class Codes: C07C 41/26 by introduction of hydroxy or O-metal groups
• CPC Class Codes: C07C 41/30 by increasing the number of carbon atoms, e.g. by oligomerisation
• CPC Class Codes: C07C 43/215 having unsaturation outside the six-membered aromatic rings
• CPC Class Codes: C07C 43/23 containing hydroxy or O-metal groups
• CPC Class Codes: C07C 45/41 by hydrogenolysis or reduction of carboxylic groups or functional derivatives thereof
• CPC Class Codes: C07C 45/455 with carboxylic acids or their derivatives
• CPC Class Codes: C07C 45/673 by change of size of the carbon skeleton
• CPC Class Codes: C07C 45/68 by increase in the number of carbon atoms
• CPC Class Codes: C07C 45/74 combined with dehydration
• CPC Class Codes: C07C 47/575 containing ether groups, groups, groups, or groups
• CPC Class Codes: C07C 49/248 having unsaturation outside the aromatic rings
• CPC Class Codes: C07C 49/255 containing ether groups, groups, groups, or groups
• CPC Class Codes: C07C 49/577 containing ether groups, groups, groups, or groups
• CPC Class Codes: C07C 51/09 from carboxylic acid esters or lactones
• CPC Class Codes: C07C 59/64 : containing six-membered aromatic rings
• CPC Class Codes: C07C 67/00 : Preparation of carboxylic acid esters
• CPC Class Codes: C07C 67/08 : by reacting carboxylic acids or symmetrical anhydrides with the hydroxy or O-metal group of organic compounds
• CPC Class Codes: C07C 67/333 : by isomerisation; by change of size of the carbon skeleton introduction or elimination of carboxyl groups C07C67/313, C07C67/32
• CPC Class Codes: C07C 69/533 : Monocarboxylic acid esters having only one carbon-to-carbon double bond
• CPC Class Codes: C07C 69/734 : Ethers
• CPC Class Codes: C07C 69/757 : having any of the groups OH, O—metal, —CHO, keto, ether, acyloxy, groups, groups, or in the acid moiety
• CPC Class Codes: C07D 311/80 : Dibenzopyrans; Hydrogenated dibenzopyrans

Abstract

Provided are synthesis processes and intermediates for preparing cannabinoids and analogs.

Claims

1. A process for the preparation of a compound of formula (I), a racemate or a stereoisomer thereof,

2. The process of claim 1, wherein step (a) is present.

3. The process of claim 2, further comprising the step of reacting a compound of formula (IV) with compound of formula (V) to produce the compound of formula (II)

4. The process of claim 3, further comprising the step of converting a compound of formula (VI) to the compound of formula (IV)

5. The process of claim 4, further comprising converting the steps of converting the compound of formula (VI) to a compound of formula (IV′

), and reducing the compound of formula (IV′

) to the compound of formula (IV)

6. The process of claim 2, wherein step (a) comprises mixing potassium bis(trimethylsilyl)amide (KHMDS) with the compound of formula (II).

7. The process of claim 1, wherein R³ is —

(CH₂)₄-CH₃.

8. The process of claim 1, wherein R¹ and R⁵ are —

OCH₃.

9. The process of claim 1, wherein R⁶ and R⁷ are each —

CH₃.

10. The process of claim 1, wherein R⁸ is hydroxyl, —

CH₃, or —

OCH₃.

11. The process of claim 1, wherein step (b) comprises mixing the compound of formula (III) with (1,3 -Bi s(2,4, 6-trimethylphenyl)-2-imidazolidinylidene)dichloro(phenylmethylene)(tricyclohexylphosphine)ruthenium.

12. A process for producing a cannabinoid, the process comprising converting the compound of formula (I) according to claim 1 to a compound of formula (VII)

13. The process of claim 12, wherein R⁸ is C₁-C₁₀ alkoxy.

14. The process of claim 12, wherein the cannabinoid is Δ

⁹-tetrahydrocannabinol (THC).

15. A process for producing a cannabinoid, the process comprising converting the compound of formula (I) according to claim 1 to a compound of formula (VIII)

16. The process of claim 15, wherein R⁸ is C₁-C₁₀ alkyl.

17. The process of claim 15, wherein the cannabinoid is cannabidiol (CBD).

18. A compound of formula (II), a racemate or a stereoisomer thereof,

19. The compound of claim 18, wherein R³ is —

(CH₂)₂-CH₃ or —

(CH₂)₄-CH₃.

20. A compound of formula (III), a racemate or a stereoisomer thereof,

21. The compound of claim 20, wherein R³ is —

(CH₂)₂-CH₃ or —

(CH₂)₄-CH₃.