Synthesis of cannabinoids

• US 10,640,482 B2
• Filed: 06/29/2018
• Issued: 05/05/2020
• 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
• Primary Examiner(s): Bahta, Medhanit W
• Application Number:
  US16/024,368
• Publication Number:
  US 20190023680A1
• Time in Patent Office: 676 Days
• Field of Search: None
• 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),

2. The process of claim 1, further comprising the step of reacting a compound of formula (IV-a) with a compound of formula (V) to produce the compound of formula (II-a)

3. The process of claim 2, further comprising the step of converting a compound of formula (VI) to the compound of formula (IV-a)

4. The process of claim 3, further comprising 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-a)

5. The process of claim 1, wherein step (a) comprises mixing potassium bis(trimethylsilyl)amide (KHMDS) with the compound of formula (II-a).

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

(CH₂)₄—

CH₃.

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

OCH₃.

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

CH₃.

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

CH₃, or —

OCH₃.

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

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

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