Description:FIELD OF THE INVENTION
The present application provides an improved process for the preparation of Bempedoic acid or its pharmaceutically acceptable salts in substantially pure form and high yield, suitable for commercial scale.

BACKGROUND OF THE INVENTION
Bempedoic acid, is an improved therapeutic approach for low-density lipoprotein cholesterol (LDL-C) lowering, inhibits adenosine triphosphate citrate lyase (ACL), an enzyme involved in fatty acid and cholesterol synthesis. Bempedoic acid (NEXLITOL) and Bempedoic acid combination with Ezitimibe (NEXLIZET) were approved by USFDA on 20 February 2020 and 26 February 2020 respectively.
Bempedoic acid having the chemical name of 8-Hydroxy-2,2,14,14-tetramethyl pentadecanedioic acid and representing by the below mentioned structure of formula (I):

Formula (I)
Bempedoic acid and its process for the preparation was first disclosed in US 7335799 by Esperion Therapeutics. The schematic representation of the disclosed process was mentioned below.

The process disclosed in the ‘799 patent is having lot of drawbacks like obtaining low yields with respective to intermediates and final compounds. In stage 1 of the process, the formation of below mentioned impurity was observed when 1, 5 dibromo pentane was reacted with ethyl isobutyrate in presence of strong base like LDA.

The process involves the excessive usage of (4.3 Equivalents) sodium borohydride (NaBH4) in the keto reduction step corresponding to starting material.
Bempedoic acid obtained in low yield of 60%, purity having 83% and the nature of the compound is in viscous oily form. The viscous oil nature and low purity Bempedoic acid is not a suitable material for pharmaceutical formulation.
The publication WO2020194152 A1 discloses a process for the preparation of Bempedoic acid which discloses the usage of Sodium borohydride (NaBH4) in higher equivalents (2.8 Equivalents) in the keto reduction step with respective to starting material.
The publication WO2020257571 A1discloses the below process for the preparation of Bempedoic acid. The process involves additional purification methods which involves the usage of large quantities of silica gel and solvent exchanges to get pure form of Bempedoic Acid.

Therefore, still there is need for the development of commercially viable, cost-effective process for the preparation of purest form of Bempedoic acid, which will be suitable for pharmaceutical formulation.

SUMMARY OF THE INVENTION
The present invention provides an improved process for the preparation Bempedoic acid or its pharmaceutically acceptable salts of formula (I), which is cost effective and suitable for industrial production.
In an aspect of the present application provides an improved process for preparation of Bempedoic acid of formula (I)

Formula (I)
which comprises
a) reacting 1-bromo-5-chloropentane of formula (IIa) or 1-chloro-5-iodopentane formula (IIb);

formula (IIa) formula (IIb)
with ethyl isobutyrate in presence of a base and in a suitable solvent to form an ethyl 7-chloro-2,2-dimethylheptanoate compound of formula (III);

formula (III)
b) reacting compound of formula (III) with salt of formula [M] [A] in a suitable solvent to form a compound of formula (IV); wherein [M] is selected from the group consisting of Li, Na, K, NH4 and [A] is selected from the group consisting of Br or I;

formula (IV)
c) reacting compound of formula (IV) with p-toluene sulfonyl methyl isocyanide (TosMIC) in presence of a base, and in suitable solvent to form compound of formula (V); wherein the compound of formula (V) is not isolated;

formula (V)
d) reacting compound of formula (V) with an acid and in suitable solvent to form a keto ester compound of formula (VI);

formula (VI)
e) reacting keto ester compound of formula (VI) with an ester hydrolysing agent in a suitable solvent to form keto acid compound of formula (VII);

formula (VII)
f) reacting keto acid compound of formula (VII) with keto reducing agent in presence of base and in a suitable solvent to form Bempedoic acid compound of formula (I);
g) optionally purifying the Bempedoic acid of formula (I) in a suitable solvent.
In another aspect the present invention provides, crystalline form of Bempedoic acid characterized by powder X-ray diffraction pattern shown in the Figure 1.
In another aspect, the present invention provides crystalline form of Bempedoic acid characterized by its PXRD pattern having one or more peaks at 5.10, 10.28, 15.45, 17.27, 17.54, 17.90, 18.23, 18.69, 19.53, 20.35, 20.67, 21.82, 22.55 and 27.55 ± 0.2 degrees 2θ.

BRIEF DESCRIPTION OF THE DRAWINGS
Figure 1 is the characteristic powder X-ray diffraction (XRD) pattern of Bempedoic
acid obtained as per the present invention.

DETAILED DESCRIPTION OF THE INVENTION
In one embodiment the present invention particularly describes process for the preparation of Bempedoic acid of formula (I)

formula (I)
In one embodiment the following scheme- 1 describe the process for the preparation of Bempedoic Acid of formula (I).

Scheme-1
In one embodiment stage (a) of the present process involves, reacting 1-bromo-5-chloropentane of formula (IIa) or 1-chloro-5-iodopentane (IIb) with ethyl isobutyrate in presence of base in a suitable solvent to provide ethyl 7-chloro-2,2-dimethylheptanoate of formula (III); wherein the suitable base is selected from LDA, Li metal/Diisopropyl amine, sodium hexamethyldisilazide, lithium hexamethyldisilazide; and the suitable solvent is selected from ethers or hydrocarbons or mixtures thereof; preferably the ether solvents are tetrahydrofuran, methyl tertiary butyl ether or mixture of both;
In another embodiment stage (b) of the present process involves, reacting ethyl 7-chloro-2,2-dimethylheptanoate of formula (III) with metal halide salts in suitable solvent to form an ethyl 7-iodo-2,2-dimethylheptanoate compound of formula (IV); wherein the metal halides are selected from Sodium Iodide, Lithium Iodide, potassium iodide, sodium bromide, Lithium bromide, potassium bromide and the solvents are selected from acetone, methyl ethyl ketone or mixtures thereof.
In another embodiment step (c) of the present process involves, reacting compound ethyl 7-iodo-2,2-dimethylheptanoate of formula (IV) with p-toluene sulfonyl methyl isocyanide (TosMIC) in presence of base in a suitable solvent to form a TosMIC adduct compound of formula (V), wherein the compound of formula (V) is not isolated, where in the base is selected from sodium hydride, potassium hydride, sodium amide, lithium amide sodium methoxide, potassium methoxide, sodium t-butoxide; most preferable base is sodium hydride or sodium methoxide; and the solvent is selected from ethers, ketones, amides, hydrocabons, sulphoxides or combination thereof; and preferable solvents are dimethyl acetamide, dimethyl sulphoxide, toluene or mixtures thereof;
In another embodiment the product of the step (c) of compound of formula (V) is not isolated proceeds to the next step.
In another embodiment step (d) of the present process involves, reacting compound of formula (V) with an acid in a suitable solvent to form diethyl 2,2,14,14-tetramethyl-8-oxopentadecanedioate a compound of formula (VI); wherein the suitable acid is hydrochloric acid, sulphuric acid or acetic acid and suitable solvent is etheric solvents like diethyl ether, di isopropyl ether, methyl tertiary butyl ether, or hydrocarbon solvents like hexane or cyclohexane. The most preferable solvent is methyl tertiary butyl ether, and the corresponding most preferable acid is hydrochloric acid.
In another embodiment step (e) of the present process involves, reacting a keto ester of compound of formula (VI) with suitable ester hydrolysing reagent in presence of a suitable solvent gives a keto acid of compound of formula (VII); wherein the suitable ester hydrolysing agent is selected from sodium hydroxide, potassium hydroxide, lithium hydroxide or calcium hydroxide; wherein the suitable solvent is selected from methanol, ethanol, ethylene glycol, 1-propanol, 2-propanol, 2-methoxyethanol, 1 -butanol, 2-butanol, iso-butyl alcohol, t-butyl alcohol and glycerol. The most preferable solvent is ethanol, and the corresponding most preferable base is sodium hydroxide.
In another embodiment step (e) of the present process involves the removing of impurities like unreacted keto ester of compound of formula (IV) or partially converted mono keto ester (14-(ethoxycarbonyl)-2,2,14-trimethyl-8-oxopentadecanoic acid); wherein after completion of reaction, the reaction mass was dissolved in water and ethylacetate was added and separated the organic layer to remove unwanted impurities. pH of the aqeous layer was acidified to obtained pure form of keto acid compound of formula (VII).
In another embodiment Step (f) of the present process involves, reducing keto acid of compound of formula (VII) with a suitable keto reducing agent in presence of suitable solvent gives Bempedoic acid of compound of formula (I); wherein the suitable keto reducing agent is Sodium borohydride, Sodium cyano borohydride, sodium triacetoxy boro hydride, potassium borohydride; and the suitable base is sodium hydroxide, potassium hydroxide, lithium hydroxide or calcium hydroxide ; and the suitable solvent is methanol, ethanol, and isopropanol. The most preferable keto reducing agent is Sodium borohydride; preferable base is sodium hydroxide, and the most preferable solvent is ethanol or isopropanol.
In another embodiment Step in (f) of the present process the ratio of keto acid compound of formula (VII) to the keto reducing agent is 1: ≤ 0.25.
In another embodiment Bempedoic acid of formula (I) is optionally purified by using a suitable solvent; wherein the suitable solvent is selected from diethyl ether, methyl tertiary butyl ether, acetone, cyclohexane, ethyl acetate, acetonitrile, ethanol, methanol, hexane, water, or mixtures thereof. The most preferable solvent is acetone and hexane.
In another embodiment, the present invention provides crystalline form of bempedoicacid characterized by powder X-ray diffraction pattern shown in the Figure 1.
In another embodiment, the present invention provides crystalline form of bempedoic
acid characterized by its PXRD pattern having one or more peaks at 5.10, 10.28, 15.45, 17.27, 17.54, 17.90, 18.23, 18.69, 19.53, 20.35, 20.67, 21.82, 22.55 and 27.55 ± 0.2 degrees 2θ.
In another embodiment the present invention provides method of crystallizing bempedoic acid from a suitable solvent selected from acetone, ethyl acetate, hexane, acetonitrile, or mixtures thereof.
In another embodiment the below are the abbreviations are used in the specification.
THF-Tetrahydrofuran, MTBE-Methyl tertiary butyl ether, g- Grams, LDA-Lithium diisopropyl amide, Sodium HMDS- Sodium heaxamethyl disilazane, mL-milliliters, °C- degrees centigrade, Eq-Equivalent, GC-Gas chromatography, HCl-Hydrochloric acid, Na2SO4-Sodium Sulphate, DMSO-Dimethyl Sulphoxide, DMAc- Dimethyl acetamide, Mg2SO4-Magnesium Sulphate, TLC-Thin layer Chromatography, GC- Gas Chromatography, HPLC-High performance Liquid Chromatography, PXRD- Powder X-ray Diffraction,
EXAMPLES
Example 1
Preparation of ethyl 7-chloro-2,2-dimethylheptanoate:

Method 1:
Charged THF (100 mL) into flask then added Diisopropylamine (82 g, 1.5 eq) and cool to 50 to -55 °C then butyl lithium (300 mL) in hexanes was added into reaction mass at -50 to - 55 °C. Raise the reaction mass temperature up to – 30 to - 40°C. After stirring for 10 minutes, Ethyl isobutyrate (78.3 g,1.25 eq) was added over period of 10 minutes, maintaining the temperature at −20 to −25° C. At the end of the addition, the mixture was stirred for 15 minutes, maintaining the temperature at −20 to −25° C, slightly hazy solution was formed. Bromochloropentane (100 g) was added by maintaining temperature at −20 to −25° C to give clear light brown solution. After stirring for 10 hours at 0 to -5° C., the reaction mass temperature was raised to 20° C. The reaction mixture was quenched with pre-cooled (1° C.) 14% HCl over 20 minutes, keeping the temperature below 15° C. The final pH was 1.0. The reaction mixture was then allowed to settle, and organic layer was separated dried over Na2SO4 and concentrated under vacuum yields 118 gm of Ethyl 7-chlorom-2,2-dimethylheptanoate. Purity by GC: 97.3%.
Method 2:
Sodium HMDS (550 mL, 1.2eq) in THF was added to THF (500 mL) into flask at -30 to - 20°C under nitrogen atmosphere. After stirring for 10 minutes, Ethyl isobutyrate (78 gm, 1.21 eq) was added over period of 10 minutes at the same temperature. After maintaining the reaction at −10 to −15° C for 15 min, Bromochloropentane (100 gm, 1 eq) was added by maintaining temperature at same temperature to give clear light brown solution. After stirring for 10 hours at 0 to -5° C., the solution was warmed to 20° C to give a viscous dark brown solution. After completion of the reaction, the reaction mass was cooled to −15° C, then a pre-cooled (1° C.) 14% HCl over a period of 20 minutes, keeping the temperature below 15° C. The organic layer was separated dried over Na2SO4 and concentrated under vacuum yields 112 gm of Ethyl 7-chloro-2,2-dimethylheptanoate.
Example 2:
Preparation of ethyl 7-iodo-2,2-dimethylheptanoate

Method 1:
To solution of Ethyl 7-chloro-2,2-dimethylheptanoate (112 gm. 1 eq), in ethyl methyl ketone (200 mL) was added Sodium Iodide (160 gm, 2.2 eq). The reaction mass was heated to reflux temperature and maintained at the same temperature for 40 hrs. After completion of the reaction sodium thiosulphate solution was added to the reaction mass. The organic layer was separated dried over Na2SO4 and concentrated under vacuum reduced pressure to obtain desired product Ethyl 7-iodo-2,2-dimethylheptanoate (130 gm). Purity: 96.5%.
Method 2:
To solution of Ethyl 7-chloro-2,2-dimethylheptanoate (112 gm. 1 eq), in ethyl methyl ketone (200 mL) was added ammonium Iodide (160 gm, 2.2 eq). The reaction mass was heated to reflux temperature and maintained at the same temperature for 40 hrs. After completion of the reaction sodium thiosulphate solution was added to the reaction mass. The organic layer was separated dried over Na2SO4 and concentrated under vacuum reduced pressure to obtain desired product Ethyl 7-iodo-2,2-dimethylheptanoate (128 gm). Purity: 97.2%.
Example 3
Preparation of 2,2,14,14-tetramethyl-8-oxo-pentadecanedioic acid diethyl ester

Method 1:
Under Nitrogen atmosphere, to a solution of Ethyl -7-iodo-2,2- dimethylheptanoic acid ethyl ester (100 g, 1.0 eq), p- Toluenesulfonyl methyl isocyanide (33 g, 0.55eq) in DMAc (200 mL) at -20 to -15°C was added sodium tert-butoxide (60 g, 2.2 eq) in DMAc at –20 to -15°C over a period of 2 hrs. The reaction mixture was stirred at room temperature for 2 h. The temperature of the reaction of the reaction mass was raised to 0- to -5°C and maintained at same temperature until the completion of the reaction. After completion of the reaction water (300 mL) was added to the reaction mass. The product was extracted with hexane (500 mL). The organic layer was washed with water (200 mL) and separated, and the organic layer was cool to 0-5°C. To the organic layer hydrochloric acid (30 mL) was added and the mixture was stirred at room temperature for 1h. The solution was quenched with 30% NaOH solution and the organic layer was separated dried over Na2SO4 and concentrated under vacuum gives 2,2,14,14-tetramethyl-8-oxo-pentadecanedioic acid diethyl ester (52 g).
Method 2:
Under Nitrogen atmosphere, to a solution of Ethyl -7-iodo-2,2- dimethylheptanoic acid ethyl ester (100 g, 1.0 eq), p- Toluenesulfonyl methyl isocyanide (33 g, 0.55 eq) in anhydrous DMSO (200 mL), was added sodium hydride (60 g, 1.5 eq) as lot wise at 10 – 150C. The reaction mixture was stirred at room temperature for 2.0 h and quenched with ice-water (300 mL). The product was extracted with hexane (500 mL). The organic layers were washed with water (200 mL) and cool to 10-15°C. To the organic layer was added concentrated hydrochloric acid (20.0 mL) and the mixture was stirred at room temperature for 1h. The solution was quenched with 30% NaOH solution and the organic layer was separated dried over Na2SO4 and concentrated under vacuum gives 2,2,14,14-tetramethyl-8-oxo-pentadecanedioic acid diethyl ester (50 gm)
Method 3:
Under Nitrogen atmosphere, to a solution of Ethyl -7-iodo-2,2- dimethylheptanoic acid ethyl ester (100 g, 1.0 eq), p- Toluenesulfonyl methyl isocyanide (33 g, 0.55 eq) in DMAc (200 mL), was added sodium methoxide (60 g, 2.2 eq) as lot wise at 10 – 150C. The product was extracted with hexane (500 mL). The organic layers were washed with water (200 mL) and cool to 10-150C. To the organic layer was added concentrated hydrochloric acid (20.0 mL) and the mixture was stirred at room temperature for 1h. The solution was quenched with 30% NaOH solution and the organic layer was separated dried over Na2SO4 and concentrated under vacuum gives 2,2,14,14-tetramethyl-8-oxo-pentadecanedioic acid diethyl ester (51 gm)
Example 4
Preparation of 2,2,14,14-tetramethyl-8-oxopentadecanedioic acid

Method 1:
A solution of Sodium hydroxide (15 g, 5.9 eq) in water (100 mL) was added to a solution of 2,2,14,14-tetramethyl-8-oxo-pentadecanedioic acid diethyl ester (25 g, 1 eq) in ethanol (100 mL), the reaction mixture was heated to reflux until it completes. After completion of the reaction distil the solvent under vacuum and charged with water (200 mL). The aqueous solution was washed with ethyl acetate (20 mL) and the organic layer was separated. The aqueous layer was acidified to pH 2 with concentrated hydrochloric acid (100 mL) and extracted with MTBE (2 x 50 mL). The combined organic layers were dried over Mg2SO4 and concentrated under vacuum to give the crude product. The crude material was crystallized from ethyl acetate to give 2,2,14,14-tetramethyl-8-oxopentadecanedioic acid (18 g, 89 %) as white crystals. Purity: 99.0%.
Method 2:
A solution of Potassium hydroxide (14 g, 4.9 eq) in water (100 mL) was added to a solution of 2,2,14,14-tetramethyl-8-oxo-pentadecanedioic acid diethyl ester (25 g, 1 eq) in ethanol (100 mL), the reaction mixture was heated to reflux until it completes. After completion of the reaction distil the solvent under vacuum and charged with water (200 mL). The aqueous solution was washed with ethyl acetate (20 mL) and the organic layer was separated. The aqueous layer was acidified to pH 2 with concentrated hydrochloric acid (100 mL) and extracted with methyl tert-butyl ether (2 x 50 mL). The combined organic layers were dried over Mg2SO4 and concentrated under vacuum to give the crude product. The crude material was crystallized from ethyl acetate to give 2,2,14,14-tetramethyl-8-oxopentadecanedioic acid (18.3 g, 90 %) as white crystals. Purity: 99.3%.
Example 5
Preparation of 8-hydroxy-2,2,14,14-tetramethylpentadecanedioic acid

Method 1:
2,14,14-tetramethyl-8-oxopentadecanedioic acid (20 g, 0.05 mol) and ethanol (200 mL) were added at room temperature into a 500 mL flask fitted with a magnetic stir bar and nitrogen inlet. Water (10 mL) was added into the reaction flask and the reaction mass was cooled below 10°C. Sodium borohydride (0.7 g, 0.3 eq) and Sodium hydroxide solution was added portion wise to the reaction mass at 10°C. The temperature was allowed to rise to 27 °C and the reaction mass was stirred for 2 h. The progress of the reaction was monitored by TLC. After completion of the reaction, water (100 mL) was added to the reaction mass which was then extracted with MTBE (100 mL). The combined organic layer was washed with brine solution (2X50 ml) and dried over Na2SO4. The organic layer was evaporated under reduced pressure below 45 °C to obtain crude product. The crude product was dissolved in ethyl acetate and water mixture solution and isolated as white crystals yield (80%) Purity by HPLC: 99.7%.
Method 2:
2,14,14-tetramethyl-8-oxopentadecanedioic acid (20 g, 0.05mol) and isopropylaclohol (200 mL) were added at room temperature into a 500 mL flask fitted with a magnetic stir bar and nitrogen inlet. Water (10 mL) and sodium hydroxide (6.0 g, 3.0eq) was added into the reaction flask and the reaction mass temperature raise to 75-80°C and then maintain for 20 hrs. Percentage of the starting material was monitored by HPLC. Then added Sodium borohydride (0.45 g, 0.2 eq) charge into the reaction mass was stirred for 2h at same temperature. The progress of the reaction was monitored by HPLC. After completion of the reaction, water (100 mL) was added to the reaction mass which was then extracted with MTBE (100 ml). The combined organic layer was washed with brine solution (2X50 ml) and dried over sodium sulfate. The obtained organic layer was evaporated under reduced pressure below 45 °C to obtain crude product. The crude product was dissolved in ethyl acetate and water mixture solution and isolated as white crystals yield (82%) Purity by HPLC: 99.8%.

Reaction condition Percentage of Product formed
Isopropyl alcohol, NaOH, 75-80°C,
20 hrs HPLC data shows 21 % of starting material has been converted to product, 82% of starting material was present.
NaBH4 was added maintained at same temperature for 2 hrs. Completely converted to Product Bempedoic acid

Method 3:
2,14,14-tetramethyl-8-oxopentadecanedioic acid (20 g, 0.05 mol) and isopropylaclohol (200 mL) were added at room temperature into a 500 mL flask fitted with a magnetic stir bar and nitrogen inlet. Water (10 mL) and sodium hydroxide (6.0 g, 3.0 eq) was added into the reaction flask and the reaction mass temperature raise to 75-80°C and then maintain for 20 hrs. Then added Sodium borohydride (0.45 g, 0.2 eq) charge into the reaction mass was stirred for 2h at same temperature. The progress of the reaction was monitored by TLC. After completion of the reaction, water (100 mL) was added to the reaction mass which was then extracted with MTBE (100 mL). The combined organic layer was washed with brine solution (2X50 mL) and dried over sodium sulfate. The obtained organic layer was evaporated under reduced pressure below 45 °C to obtain crude product. The crude product was dissolved in Acetone (20 mL) and added Hexanes (60.0 mL) mixture solution and isolated as white crystals yield (81%) Purity by HPLC: 99.6%.

, Claims:1. A process for the preparation of Bempedoic acid compound of formula (I)

formula (I)
which comprises
a) reacting 1-bromo-5-chloropentane of formula (IIa) or 1-chloro-5-iodopentane formula (IIb)

formula (IIa) formula (IIb)
with ethyl isobutyrate in presence of a base and in a suitable solvent to form an ethyl 7-chloro-2,2-dimethylheptanoate of formula (III);

formula (III)
b) reacting compound of formula (III) with a salt of formula [M] [A] in a suitable solvent to form a compound of formula (IV); wherein [M] is selected from the group consisting of Li, Na, K, NH4 and [A] is selected from the group consisting of Br or I;

formula (IV)
c) reacting compound of formula (IV) with p-toluene sulfonyl methyl isocyanide (TosMIC) in presence of a base, and in suitable solvent to form compound of formula (V); wherein the compound of formula (V) is not isolated;

formula (V)
d) reacting compound of formula (V) with an acid in suitable solvent to form a keto ester compound of formula (VI);

formula (VI)
e) reacting keto ester compound of formula (VI) with an ester hydrolysing agent in a suitable solvent to form keto acid compound of formula (VII);

formula (VII)
f) reacting keto acid compound of formula (VII) with keto reducing reagent in presence of base and in a suitable solvent to form Bempedoic acid compound of formula (I);
g) optionally purifying the Bempedoic acid of formula (I) in a suitable solvent.
2. The process as claimed claim 1, wherein the compound of formula (V) is not isolated.
3. The process as claimed in claim 1, wherein, in step (a) the base is selected from Li metal/Diisopropylamine, lithium diisopropyl amide, sodium hexamethyldisilazide, lithium hexamethyldisilazide; and the solvent are selected from ethers, aliphatic hydrocarbons or mixtures thereof; and the most preferable solvent is toluene, MTBE or THF or mixtures thereof; in step (b) the metal salts are selected from sodium iodide, potassium iodide, lithium iodide ammonium iodide, sodium bromide, potassium bromide or lithium bromide and the suitable solvent is selected from acetone or ethyl methyl ketone; in step (c) the suitable base is selected from sodium methoxide, potassium tert-butoxide, sodium hydride or cesium carbonate; the suitable solvent is dimethyl acetamide or dimethyl sulphoxide; in step (d) the suitable acid is hydrochloric acid and the suitable solvent is hexane or MTBE; in step (e) the suitable ester hydrolysing agent is sodium hydroxide, potassium hydroxide, lithium hydroxide or calcium hydroxide; and the suitable solvent is ethanol, methanol or isopropanol; in step (f) the suitable keto reducing agent is Sodium borohydride, Sodium cyano borohydride, sodium triacetoxy boro hydride, potassium borohydride; base is sodium hydroxide, potassium hydroxide, lithium hydroxide or calcium hydroxide and the suitable solvent is methanol, ethanol, and isopropanol.
4. The process as claimed claim 1, for the preparation of compound of formula (III)

Formula (III)
which comprises reacting 1-bromo-5-chloropentane of formula (IIa) or 1-chloro-5-iodopentane of formula (IIb) with ethyl isobutyrate in presence of Li metal/Diisopropylamine, lithium diisopropyl amide, sodium hexamethyldisilazide, or lithium hexamethyldisilazide in a solvent like THF, MTBE, toluene or mixtures thereof.
5. A process for the preparation of compound of formula (III)

Formula (III)
which comprises
reacting 1-bromo-5-chloropentane of formula (IIa) or 1-chloro-5-iodopentane of formula (IIb) with ethyl isobutyrate in presence of sodium hexamethyldisilazide and solvent like MTBE or THF.
6. A process for the preparation of Bempedoic acid compound of formula (I)

formula (I)
which comprises reducing the keto acid compound of formula (VII) with a suitable keto reducing agent and in presence of a suitable base and solvent; wherein the keto reducing reagent is selected from Sodium cyano borohydride, sodium triacetoxy boro hydride, potassium borohydride; and the base is sodium hydroxide, potassium hydroxide, lithium hydroxide or calcium hydroxide; the suitable solvent is methanol, ethanol, or isopropyl alcohol.
7. The process as claimed in claim 5, most preferable keto reducing agent is sodium borohydride, preferable base is sodium hydroxide, and the most preferable solvent is isopropyl alcohol.
8. The process as claimed claim 6, the mole of ratio of compound of formula (VII) to the keto reducing agent is 1: < 0.25.
9. The process as claimed in claim (1), for the purification of bempedoic acid compound of formula (I), which comprise of crystallizing bempedoic acid from a suitable solvent selected from acetone, ethyl acetate, hexane, acetonitrile, or mixtures thereof.
10. The process as claimed in claim 9, preferable solvent is acetone or hexane or mixtures thereof.