The present invention relates to an improved process for the preparation of bempedoic acid or its pharmaceutically acceptable salts. The present invention also provides novel salts of a compound of Formula II, a process for its preparation, and its use for the preparation of bempedoic acid or its pharmaceutically acceptable salts.
Background of the Invention
Bempedoic acid is chemically known as 8-hydroxy-2,2,14,14-tetramethyl-
pentadecanedioic acid, and is represented by Formula I.
OH OH
J CH3 °H H3C I
H3C CH3
Formula I
Bempedoic acid is an adenosine triphosphate-citrate lyase (ACL) inhibitor indicated as an adjunct to diet and maximally tolerated statin therapy for the treatment of adults with heterozygous familial hypercholesterolemia or established atherosclerotic cardiovascular disease who require additional lowering of LDL-C.
U.S. Patent No. 7,335,799 describes a process for the preparation of bempedoic acid.
PCT Publication No. WO2020/141419 discloses novel pharmaceutically acceptable organic and inorganic salts of bempedoic acid and processes for their preparation.
Indian Patent Application No. 201941011853 discloses a process for the preparation of bempedoic acid.
Summary of the Invention
The present invention relates to an improved process for the preparation of bempedoic acid or its pharmaceutically acceptable salts. The present invention further provides novel salts of a compound of Formula II, a process for its preparation, and its use for the preparation of bempedoic acid or its pharmaceutically acceptable salts.
The present invention provides environment friendly, cost-effective, easy to handle, and industrially advantageous process for the preparation of bempedoic acid. The process of the present invention provides bempedoic acid having a chromatographic purity of about 99%.
2

Detailed Description of the Invention
The term "about," as used herein, refers to any value within the range defined by a number up to ±10% of the value.
The term "room temperature," as used herein, refers to a temperature in the range of 25°Cto35°C.
The term "Ci-6 alkyl," as used herein, refers to methyl, ethyl, n-propyl, iso-propyl, n-butyl, iso-butyl, sec-butyl, tert-butyl, n-pentyl, neo-pentyl, iso-pentyl, sec-pentyl, n-hexyl, iso-hexyl, 2,3-dimethylbutyl, or neo-hexyl.
The term "aryl," as used herein, refers to a monocyclic aromatic hydrocarbon. An example of an aryl is unsubstituted or substituted phenyl.
The term "aralkyl," as used herein, refers to a methylene substituted aryl group. An example of an aralkyl is benzyl.
The term "base," as used herein, refers to organic base selected from the group
consisting of trimethylamine, triethylamine, tert-butylamine, meglumine, ethylenediamine,
dimethylamine, diethylamine, diisopropylamine, diisopropylethylamine, diisobutylamine.
benzylamine, ethanolamine, diethanolamine, triethanolamine, phenylethylamine,
dicyclohexylamine, piperazine, pyridine, quinoline, diphenylpyrrolidine, 1,2-
dibenzylpyrrolidine, 2-(anilinomethyl)pyrrolidine, 2-bis(3,5-dimethylphenyl)methyl
pyrrolidine, diphenyl-2-pyrrolidinemethanol, prolinol, Af-methyl-3-phenyl-propan-l -amine, l,2-diphenyl-l,2-ethylenediamine, 4,5-diphenyl imidazolidine, l,8-diazabicyclo[5.4.0]undec-7-ene, l,5-diazabicyclo[4.3.0]non-5-ene, l,4-diazabicyclo[2.2.2] octane, and amino acids.
A first aspect of the present invention provides a process for the preparation of a compound of Formula II;
H3C CH3 ,Salt
Formula II
wherein the salt is selected from the group consisting of trimethylamine, triethylamine, tert-butylamine, meglumine, ethylenediamine, dimethylamine, diethylamine, diisopropylamine,
3

diisopropylethylamine, diisobutylamine, benzylamine, ethanolamine, diethanolamine, triethanolamine, phenylethylamine, dicyclohexylamine, piperazine, pyridine, quinoline, diphenylpyrrolidine, 1,2-dibenzylpyrrolidine, 2-(anilinomethyl)pyrrolidine, 2-bis(3,5-dimethylphenyl)methylpyrrolidine, diphenyl-2-pyrrolidinemethanol, prolinol, JV-methyl-3-phenyl-propan-1 -amine, l,2-diphenyl-l,2-ethylenediamine, 4,5-diphenylimidazolidine, 1,8-diazabicyclo[5.4.0]undec-7-ene, 1,5-diazabicyclo[4.3.0]non-5-ene, 1,4-diazabicyclo[2.2.2] octane, and amino acids; and
R1 and R2 are selected from the group consisting of hydrogen, Ci-6 alkyl, aryl, and aralkyl, with the proviso that R1 and R2 are not both Ci-6 alkyl, aryl, and aralkyl;
comprising treating a compound of Formula III
O 0

H3C CH3
Formula III
with a base in a solvent.
A second aspect of the present invention provides a process for the preparation of bempedoic acid of Formula 1 or its pharmaceutically acceptable salts;


OH OH
H3C CH3
Formula I
comprising
a) treating a compound of Formula III
o o

Formula III
with a base in a solvent to obtain a compound of Formula II;
4


o o
H3C CH, 'bdu
Formula II
wherein the salt is selected from the group consisting of trimethylamine, triethylamine, tert-butylamine, meglumine, ethylenediamine, dimethylamine, diethylamine, diisopropylamine, diisopropylethylamine, diisobutylamine, benzylamine, ethanolamine, diethanolamine, triethanolamine, phenylethylamine, dicyclohexylamine, piperazine, pyridine, quinoline, diphenylpyrrolidine, 1,2-dibenzylpyrrolidine, 2-(anilinomethyl)pyrrolidine, 2-bis(3,5-dimethyl phenyl)methylpyrrolidine, diphenyl-2-pyrrolidinemethanol, prolinol, Af-methyl-3-phenyl-propan-1-amine, l,2-diphenyl-l,2-ethylenediamine, 4,5-diphenylimidazolidine, 1,8-diazabicyclo[5.4.0]undec-7-ene, l,5-diazabicyclo[4.3.0]non-5-ene, 1,4-diazabicyclo[2.2.2] octane, and amino acids; and
R1 and R2 are selected from the group consisting of hydrogen, Ci-6 alkyl, aryl, and aralkyi, with the proviso that R1 and R2 are not both Ci-6 alkyl, aryl, and aralkyi;
b) treating the compound of Formula II with an acid in a solvent to obtain a compound of Formula III; and
c) converting the compound of Formula III to bempedoic acid of Formula I or its pharmaceutically acceptable salts.
A third aspect of the present invention provides a process for the preparation of a compound of Formula Ha;


OH OH
H3C CH3
.salt
Formula Ha
wherein the salt is selected from the group consisting of trimethylamine, triethylamine, tert-butylamine, meglumine, ethylenediamine, dimethylamine, diethylamine, diisopropylamine, diisopropylethylamine, diisobutylamine, benzylamine, ethanolamine, diethanolamine, triethanolamine, phenylethylamine, dicyclohexylamine, piperazine, pyridine, quinoline, diphenylpyrrolidine, 1,2-dibenzylpyrrolidine, 2-(anilinomethyl)pyrrolidine, 2-bis(3,5-dimethyl
5

phenyl)methylpyrrolidine, diphenyl-2-pyrrolidinemethanol, prolinol, Af-methyl-3-phenyl-propan-1-amine, l,2-diphenyl-l,2-ethylenediamine, 4,5-diphenylimidazolidine, 1,8-diaza bicyclo[5.4.0]undec-7-ene, l,5-diazabicyclo[4.3.0]non-5-ene, 1,4-diazabicyclo [2.2.2]octane, and amino acids; comprising treating a compound of Formula Ilia


OH

OH

Formula Ilia
with a base in a solvent.
A fourth aspect of the present invention provides a process for the preparation of bempedoic acid of Formula I or its pharmaceutically acceptable salts;
OH OH

Formula I
a) treating a compound of Formula Ilia


OH

OH

Formula Ilia
with a base in a solvent to obtain a compound of Formula Ha;
OH
OH
o
.salt
Formula Ila
wherein the salt is selected from the group consisting of trimethylamine, triethylamine, tert-butylamine, meglumine, ethylenediamine, dimethylamine, diethylamine, diisopropylamine, diisopropylethylamine, diisobutylamine, benzylamine, ethanolamine, diethanolamine, triethanolamine, phenylethylamine, dicyclohexylamine, piperazine, pyridine, quinoline, diphenylpyrrolidine, 1,2-dibenzylpyrrolidine, 2-(anilinomethyl)pyrrolidine, 2-bis(3,5-
6

dimethylphenyl)methylpyrrolidine, diphenyl-2-pyrrolidinemethanol, prolinol, iV-methyl-3-phenyl-propan-1-amine, l,2-diphenyl-l,2-ethylenediamine, 4,5-diphenylimidazolidine, 1,8-diazabicyclo[5.4.0]undec-7-ene, l,5-diazabicyclo[4.3.0]non-5-ene, l,4-diazabicyclo[2.2.2] octane, and amino acids;
b) treating the compound of Formula Ha with an acid in a solvent to obtain a compound of Formula Ilia; and
c) converting the compound of Formula Ilia to bempedoic acid of Formula I or its pharmaceutically acceptable salts.
A fifth aspect of the present invention provides a compound of Formula II;
o

Formula II
wherein the salt is selected from the group consisting of trimethylamine, triethylamine, tert-butylamine, meglumine, ethylenediamine, dimethylamine, diethylamine, diisopropylamine, diisopropylethylamine, diisobutylamine, benzylamine, ethanolamine, diethanolamine, triethanolamine, phenylethylamine, dicyclohexylamine, piperazine, pyridine, quinoline, diphenylpyrrolidine, 1,2-dibenzylpyrrolidine, 2-(anilinomethyl)pyrrolidine, 2-bis(3,5-dimethylphenyl)methylpyrrolidine, diphenyl-2-pyrrolidinemethanol, prolinol, A^-methyl-3-phenyl-propan-1-amine, l,2-diphenyl-l,2-ethylenediamine, 4,5-diphenylimidazolidine, 1,8-diazabicyclo[5.4.0]undec-7-ene, l,5-diazabicyclo[4.3.0]non-5-ene, l,4-diazabicyclo[2.2.2] octane, and amino acids; and
R1 and R2 are selected from the group consisting of hydrogen, Ct-6 alkyl, aryl, and aralkyl, with the proviso that R1 and R2 are not both Ci-6 alkyl, aryl, and aralkyl.
A sixth aspect of the present invention provides use of a compound of Formula II;
o o
R JL / 3 II 3 \ JL R
H3C CH3 "Salt
Formula II
wherein the salt is selected from the group consisting of trimethylamine, triethylamine, tert-butylamine, meglumine, ethylenediamine, dimethylamine, diethylamine, diisopropylamine,
7

diisopropylethylamine, diisobutylamine, benzylamine, ethanolamine, diethanolamine, triethanolamine, phenylethylamine, dicyclohexylamine, piperazine, pyridine, quinoline, diphenylpyrrolidine, 1,2-dibenzylpyrrolidine, 2-(anilinomethyl)pyrrolidine, 2-bis(3,5-dimethylphenyl)methylpyrrolidine, diphenyl-2-pyrrolidinemethanol, prolinol, Af-methyl-3-phenyl-propan-1-amine, l,2-diphenyl-l,2-ethylenediamine, 4,5-diphenylimidazolidine, 1,8-diazabicyclo[5.4.0]undec-7-ene, l,5-diazabicyclo[4.3.0]non-5-ene, 1,4-diazabicyclo [2.2.2] octane, and amino acids; and
R1 and R2 are selected from the group consisting of hydrogen, Ci-6 alkyl, aryl, and aralkyl, with the proviso that R1 and R2 are not both Ci-6 alkyl, aryl, and aralkyl;
for the preparation of bempedoic acid of Formula I or its pharmaceutical^ acceptable salts.
The compound of Formula Ilia may be prepared by any method known in the art, for example, the method described in U.S. Patent No. 7,335,779.
The treatment of the compound of Formula III or Ilia with a base to obtain the compound of Formula II or Ha is carried out in a solvent.
The solvent is selected from the group consisting of alcohols, nitriles, halogenated hydrocarbons, ethers, water, and mixtures thereof. Examples of alcohols include methanol, ethanol, propanol, iso-propanol, n-butanol, and iso-butanol. An example of nitrile is acetonitrile. Examples of halogenated hydrocarbons include dichloromethane, dichloroethane, chloroform, and carbon tetrachloride. Examples of ethers include tetrahydrofuran, ethyl methyl ether, diethyl ether, diisopropyl ether, and methyl tert-butyl ether.
The treatment of the compound of Formula III or Ilia with a base is carried out in about 5 hours to about 15 hours, for example, in about 6 hours to about 10 hours.
The treatment of the compound of Formula III or Ilia with a base is carried out at room temperature.
The compound of Formula II or Ha may optionally be isolated by filtration, decantation, extraction, distillation, evaporation, chromatography, precipitation, concentration, crystallization, centrifugation, and recrystallization. The compound of Formula II or Ha may be dried using conventional techniques, for example, drying, drying under vacuum, spray drying, suck drying, air drying, or agitated thin film drying.
8

The compound of Formula II or Ha is treated with an acid to obtain a compound of Formula III or Ilia in a solvent.
The acid is selected from the group consisting of hydrochloric acid, trifluoroacetic acid, sulfuric acid, nitric acid, phosphoric acids, and methanesulfonic acid.
The solvent is selected from the group consisting of alcohols, nitriles, halogenated hydrocarbons, ethers, water, and mixtures thereof. Examples of alcohols include methanol, ethanol, propanol, iso-propanol, n-butanol, and iso-butanol. An example of nitrile is acetonitrile. Examples of halogenated hydrocarbons include dichloromethane, dichloroethane, chloroform, and carbon tetrachloride. Examples of ethers include tetrahydrofuran, ethyl methyl ether, diethyl ether, diisopropyl ether, and methyl tert-butyl ether.
The treatment of the compound of Formula II or Ha with an acid is carried out in about 30 minutes to about 10 hours, for example, in about one hour to about 5 hours.
The treatment of the compound of Formula II or Ila with an acid is carried out at room temperature.
The compound of Formula III or Ilia may optionally be isolated by filtration, decantation, extraction, distillation, evaporation, chromatography, precipitation, concentration, crystallization, centrifugation, and recrystallization. The compound of Formula III or Ilia may be dried using conventional techniques, for example, drying, drying under vacuum, spray drying, suck drying, air drying, or agitated thin film drying.
The compound of Formula III or Ilia is converted to bempedoic acid of Formula I or its pharmaceutically acceptable salts by the process known in the art, for example, as disclosed in U.S. Patent No. 7,335,799.
While the present invention has been described in terms of its specific aspects and embodiments, certain modifications and equivalents will be apparent to those skilled in the art, and are intended to be included within the scope of the present invention.
The following examples are for illustrative purposes only and should not be construed as limiting the scope of the invention in any way.
9

EXAMPLES Example 1: Preparation of dicyclohexylamine (DCHA) salt of 8-oxo-2,2,14,14-tetramethyl pentadecanedioic acid (Formula Ila)
Dicyclohexylamine (3.65 g) was added to a solution of 8-oxo-2,2,14,14-tetramethylpentadecanedioic acid (3.42 g; Formula Ilia) in methyl tert-butyl ether (18.25 ml) to obtain a suspension. The obtained suspension was stirred at room temperature for 6 hours. The suspension was then filtered, washed with methyl tert-butyl ether and dried under vacuum to obtain the title compound as a white solid. Yield: 90.8 %
Chromatographic purity: 99.5%
^NMR (CDCb, 300MHz): 8 1.13-1.28 (m, 44H), 1.44 (m, 4H), 1.61 (m, 8H), 1.76 (m, 8H), 1.95 (m, 8H), 2.35 (t, 4H), 2.78 (m, 4H), and 5.37 (brs, 4H);
13CNMR (CDCb, 300MHz): 23.8, 24.9, 25.1, 25.69, 26.07, 29.53, 31.19, 41.22, 42.4, 42.6, 52.9, 183.69, and 211.9; Mass: 341 [M-l].
Example 2: Preparation of 8-oxo-2,2,14,14-tetramethyI pentadecanedioic acid (Formula Ilia)
Dicyclohexylamine (DCHA) salt of 8-oxo-2,2,14,14-tetramethylpentadecanedioic acid (5 g; Formula Ila, obtained from Example 1) was added to a round bottom flask (RBF) at room temperature. An aqueous solution of sodium hydroxide (0.763 g of NaOH in 10 mL in water) followed by addition of dichloromethane was added to the reaction mixture and stirred for one hour. The layers were separated and the aqueous layer was washed with dichloromethane (5 mL). An aqueous hydrochloric acid was added till the pH becomes 1 to 2 and then extracted with dichloromethane (5 mL). The layers were separated and the organic layer was washed with water (2X5 mL). The organic layer was concentrated under vacuum at 40°C to obtain the title compound. Yield: 3.3 g
Example 3: Preparation of bempedoic acid
10

8-0x0-2,2,14,14-tetramethylpentadecanedioic acid (Formula Ilia; obtained from Example 2) was converted to bempedoic acid as per procedure disclosed in U.S. Patent No. 7,335,799. Chromatographic purity: 99.6%
Dated this October 05, 2021 /j
Dr. Shivani Rana (Kimia Biosciences Limited)

WE CLAIMS

A process for the preparation of a compound of Formula II;

H3C CH3
Formula II
wherein the salt is selected from the group consisting of trimethylamine, triethylamine, tert-
butylamine, meglumine, ethylenediamine, dimethylamine, diethylamine, diisopropylamine,
diisopropylethylamine, diisobutylamine, benzylamine, ethanolamine, diethanolamine,
triethanolamine, phenylethylamine, dicyclohexylamine, piperazine, pyridine, quinoline,
diphenylpyrrolidine, 1,2-dibenzylpyrrolidine, 2-(anilinomethyl)pyrrolidine, 2-bis(3,5-
dimethylphenyl)methylpyrrolidine, diphenyl-2-pyrrolidinemethanol, prolinol, Af-methyl-3-
phenyl-propan-l-amine, l,2-diphenyl-l,2-ethylenediamine, 4,5-diphenylimidazolidine,
l,8-diazabicyclo[5.4.0]undec-7-ene, l,5-diazabicyclo[4.3.0]non-5-ene, 1,4-
diazabicyclo[2.2.2] octane, and amino acids; and
R1 and R2 are selected from the group consisting of hydrogen, Ci-6 alkyl, aryl, and aralkyl, with the proviso that R1 and R2 are not both Ci-6 alkyl, aryl, and aralkyl; comprising treating a compound of Formula III

Formula III
with a base in a solvent.
2. A process for the preparation of bempedoic acid of Formula I or its pharmaceutically acceptable salts;

Formula I
comprising
a) treating a compound of Formula III
12

o o



Formula III
with a base in a solvent to obtain a compound of Formula II;
O 0
H3C CH3 ■bdu
Formula II
wherein the salt is selected from the group consisting of trimethylamine, triethylamine, tert-
butylamine, meglumine, ethylenediamine, dimethylamine, diethylamine, diisopropylamine,
diisopropylethylamine, diisobutylamine, benzylamine, ethanolamine, diethanolamine,
triethanolamine, phenylethylamine, dicyclohexylamine, piperazine, pyridine, quinoline,
diphenylpyrrolidine, 1,2-dibenzylpyrrolidine, 2-(anilinomethyl)pyrrolidine, 2-bis(3,5-
dimethyl phenyl)methylpyrrolidine, diphenyl-2-pyrrolidinemethanol, prolinol, Af-methyl-3-
phenyl-propan-1-amine, l,2-diphenyl-l,2-ethylenediamine, 4,5-diphenylimidazolidine,
l,8-diazabicyclo[5.4.0]undec-7-ene, l,5-diazabicyclo[4.3.0]non-5-ene, 1,4-
diazabicyclo[2.2.2] octane, and amino acids; and
R1 and R2 are selected from the group consisting of hydrogen, Ci-6 alkyl, aryl, and aralkyl, with the proviso that R1 and R2 are not both Ci-6 alkyl, aryl, and aralkyl;
b) treating the compound of Formula II with an acid in a solvent to obtain a compound of Formula III; and
c) converting the compound of Formula III to bempedoic acid of Formula I or its pharmaceutically acceptable salts.
3. A process for the preparation of a compound of Formula Ila;

H3C CH3
.salt
Formula Ila
wherein the salt is selected from the group consisting of trimethylamine, triethylamine, tert-butylamine, meglumine, ethylenediamine, dimethylamine, diethylamine, diisopropylamine,
13

diisopropylethylamine, diisobutylamine, benzylamine, ethanolamine, diethanolamine, triethanolamine, phenylethylamine, dicyclohexylamine, piperazine, pyridine, quinoline, diphenylpyrrolidine, 1,2-dibenzylpyrrolidine, 2-(anilinomethyl)pyrrolidine, 2-bis(3,5-dimethyl phenyl)methylpyrrolidine, diphenyl-2-pyrrolidinemethanol, prolinol, A^-methyl-3-phenyl-propan-1 -amine, l,2-diphenyl-l,2-ethylenediamine, 4,5-diphenylimidazolidine, 1,8-diaza bicyclo[5.4.0]undec-7-ene, l,5-diazabicyclo[4.3.0]non-5-ene, 1,4-diazabicyclo [2.2.2]octane, and amino acids; comprising treating a compound of Formula Ilia

Formula Ilia
with a base in a solvent.
4. A process for the preparation of bempedoic acid of Formula I or its pharmaceuticaliy acceptable salts;

Formula I
a) treating a compound of Formula Ilia


OH

OH

Formula Ilia
with a base in a solvent to obtain a compound of Formula Ha;
OH
OH
o
.salt
Formula Ila
wherein the salt is selected from the group consisting of trimethylamine, triethylamine, tert-butylamine, meglumine, ethylenediamine, dimethylamine, diethyiamine, diisopropylamine,
14

diisopropylethylamine, diisobutylamine, benzylamine, ethanolamine, diethanolamine,
triethanolamine, phenylethylamine, dicyclohexylamine, piperazine, pyridine, quinoline,
diphenylpyrrolidine, 1,2-dibenzylpyrrolidine, 2-(anilinomethyl)pyrrolidine, 2-bis(3,5-
dimethylphenyl)methylpyrrolidine, diphenyl-2-pyrrolidinemethanol, prolinol, JV-methyl-3-
phenyl-propan-1-amine, l,2-diphenyl-l,2-ethylenediamine, 4,5-diphenylimidazolidine,
l,8-diazabicyclo[5.4.0]undec-7-ene, l,5-diazabicyclo[4.3.0]non-5-ene, 1,4-
diazabicyclo[2.2.2] octane, and amino acids;
b) treating the compound of Formula Ila with an acid in a solvent to obtain a compound of Formula Ilia; and
c) converting the compound of Formula Ilia to bempedoic acid of Formula I or its pharmaceutically acceptable salts.
5. A compound of Formula II;
o o

H3C CH3 -salt
Formula II
wherein the salt is selected from the group consisting of trimethylamine, triethylamine, tert-
butylamine, meglumine, ethylenediamine, dimethylamine, diethylamine, diisopropylamine,
diisopropylethylamine, diisobutylamine, benzylamine, ethanolamine, diethanolamine,
triethanolamine, phenylethylamine, dicyclohexylamine, piperazine, pyridine, quinoline,
diphenylpyrrolidine, 1,2-dibenzylpyrrolidine, 2-(anilinomethyl)pyrrolidine, 2-bis(3,5-
dimethylphenyl)methylpyrrolidine, diphenyl-2-pyrrolidinemethanol, prolinol, Af-methyl-3-
phenyl-propan-1-amine, l,2-diphenyl-l,2-ethylenediamine, 4,5-diphenylimidazolidine,
l,8-diazabicyclo[5.4.0]undec-7-ene, l,5-diazabicyclo[4.3.0]non-5-ene, 1,4-
diazabicyclo[2.2.2] octane, and amino acids; and
R1 and R2 are selected from the group consisting of hydrogen, Ci-6 alkyl, aryl, and aralkyl, with the proviso that R1 and R2 are not both Ci-6 alkyl, aryl, and aralkyl.
6. Use of a compound of Formula II;
15


o o
H3C CH3 •hdii
Formula II
wherein the salt is selected from the group consisting of trimethylamine, triethylamine, tert-butylamine, meglumine, ethylenediamine, dimethylamine, diethylamine, diisopropylamine, diisopropylethylamine, diisobutylamine, benzylamine, ethanolamine, diethanolamine, triethanolamine, phenylethylamine, dicyclohexylamine, piperazine, pyridine, quinoline, diphenylpyrrolidine, 1,2-dibenzylpyrrolidine, 2-(anilinomethyl)pyrrolidine, 2-bis(3,5-dimethylphenyl)methylpyrrolidine, diphenyl-2-pyrrolidinemethanol, prolinol, iV-methyl-3-phenyl-propan-1-amine, l,2-diphenyl-l,2-ethylenediamine, 4,5-diphenylimidazolidine, l,8-diazabicyclo[5.4.0]undec-7-ene, l,5-diazabicyclo[4.3.0]non-5-ene, 1,4-diazabicyclo [2.2.2] octane, and amino acids; and
R1 and R2 are selected from the group consisting of hydrogen, C1-6 alkyl, aryl, and aralkyl, with the proviso that R1 and R2 are not both C1-6 alkyl, aryl, and aralkyl; for the preparation of bempedoic acid of Formula I or its pharmaceutically acceptable salts.
7. The process according to claim 1 or claim 2 or claim 3 or claim 4, wherein the base is selected from trimethylamine, triethylamine, tert-butylamine, meglumine, ethylenediamine, dimethylamine, diethylamine, diisopropylamine, diisopropylethylamine, diisobutylamine, benzylamine, ethanolamine, diethanolamine, triethanolamine, phenylethylamine, dicyclohexylamine, piperazine, pyridine, quinoline, diphenylpyrrolidine, 1,2-dibenzylpyrrolidine, 2-(anilinomethyl)pyrrolidine, 2-bis(3,5-dimethylphenyl)methyl pyrrolidine, diphenyl-2-pyrrolidinemethanol, prolinol, iV-methyl-3-phenyl-propan-l-amine, l,2-diphenyl-l,2-ethylenediamine, 4,5-diphenyl imidazolidine, 1,8-diazabicyclo[5.4.0]undec-7-ene, 1,5-diazabicyclo[4.3.0]non-5-ene, 1,4-diazabicyclo[2.2.2] octane, and amino acids.
8. The process according to claim 1 or claim 2 or claim 3 or claim 4, wherein the acid is selected from hydrochloric acid, trifluoroacetic acid, sulfuric acid, nitric acid, phosphoric acid, or methanesulfonic acid.
16

9. The process according to claim 1 or claim 2 or claim 3 or claim 4, wherein the solvent is selected from alcohols, nitriles, halogenated hydrocarbons, ethers, water, and mixtures thereof.