1. Intellectual Property Project
Brittney Blackburne
CHE 243-300
4/29/14

2. 
Dronabinol is “medical
marijuana”

Aka
'Tetrahydrocannabinol'
(THC)

Antimietic

Taken orally

Side effects

Brand names
− Marinol®
What is Dronabinol?

3. What does it treat?

Nausea/vomiting

Motion sickness

Appetite

Cancer effects

Side effects from
other drugs

4. Chemistry of Dronabinol

Molecular Formula: C21H30O2

Molecular Weight: 314.4617

Solubility: Soluble in ethanol

Boiling point: 157 °C

Other notes: Very low toxicity. Chemical
found naturally in cannabis. Represses
neurotransmitters in the brain.

5. Patent Information

Name of Patent: Synthetic route to dronabinol

Purpose: To determine a novel synthetic route for creating the compound
dronabinol, which can be distributed as an antiemetic.

Patent Number: 7,323,576

Inventors: Souza; Fabio E. S. (Mississauga, CA), Field; Jason E. (Mississauga,
CA), Pan; Ming (Mississauga, CA), Ramjit; Navindra J. (Mississauga, CA),
Tharmanathan; Tharsika (Markham, CA), Jende-Tindall; Tracey (Aurora, CA)

Assignee: Alphora Research Inc. (Mississauga, Ontario, CA)

Date of Filing: October 1, 2004

Date Patent Expires: October 1, 2024

6. Patent Information

Seven Dependent Claims

Two independent claims:
− 1. A process for preparing Dronabinol by esterifying cis-(1R,2S)-2-hydroxy-4-
methylcyclohex-3-ene carboxylic acid to form a lower alkyl ester. Then, subjecting
the lower alkyl ester to a nucleophilic addition reaction with an appropriate
organometallic compound to form cis-(3S,4R)-1-methyl-3-hydroxy-4-(2-hydroxyprop-
2-yl) cyclohex-1-ene. Finally, reacting said product with olivetol (1,3-dihydroxy-5-n-
pentylbenzene).

7. Patent Information

Seven Dependent Claims

Two independent claims:
− 1. A process for preparing Dronabinol by esterifying cis-(1R,2S)-2-hydroxy-4-
methylcyclohex-3-ene carboxylic acid to form a lower alkyl ester. Then, subjecting
the lower alkyl ester to a nucleophilic addition reaction with an appropriate
organometallic compound to form cis-(3S,4R)-1-methyl-3-hydroxy-4-(2-hydroxyprop-
2-yl) cyclohex-1-ene. Finally, reacting said product with olivetol (1,3-dihydroxy-5-n-
pentylbenzene).

8. Patent Information
− 2. A process of preparing dronabinol, which comprises the successive steps of:
(a) reacting 2-methyl-3-butyn-2-ol with acetic anhydride under acidic conditions,
followed by transition metal catalyzed rearrangement, to obtain 1-acetoxy-3-
methyl-1,3-butadiene; (b) subjecting the product to Diels-Alder reaction with
methyl acrylate to form methyl 2-acetoxy-4-methyl cyclohex-3-ene carboxylate; (c)
isolating the racemic cis isomer of product from (b) by crystallization; (d)
converting this carboxylate to racemic cis-2-hydroxy-4-methylcyclohex-3-ene carboxylic
acid; (e) resolving the racemic mixture to obtain significantly enantiomerically
enriched cis-2-hydroxy-4-methylcyclohex-3-ene carboxylic acid; (f) esterifying the
resolved product from (e) to form a lower alkyl ester (g) reacting the lower
alkyl ester with a methyl magnesium halide to form cis-menth-1-ene-3,8-diol; (h)
reacting product from (g) with olivetol to form 1,3-dihydroxy-2-[(1R,6R)-6-(2-
hydroxyprop-2-yl)-3-methylcyclohex-2-en-1-y- l]-5-n-pentylbenzene; and (i) cyclizing
the product from (h) to obtain dronabinol.

9. Questions?

10. Sources

US Patent Office

Medline Plus

Pubchem

Pubchem