DESC:FORM 2
THE PATENT ACT 1970
(39 of 1970)
&
THE PATENT RULES, 2003
COMPLETE SPECIFICATION
(See section 10 and rule 13)

“A PROCESS FOR PREPARATION OF SUBSTITUTED BENZOIC ACIDS”

SRF LIMITED, AN INDIAN COMPANY,
SECTOR 45, BLOCK-C, UNICREST BUILDING,
GURGAON – 122003,
HARYANA (INDIA)

The following specification particularly describe the invention and the manner in which it is to be performed.

FIELD OF THE INVENTION
The present invention provides a process for preparation of halogen substituted nitrobenzoic acid of formula I.

Formula I
wherein X is a halogen selected from Cl, F, Br and I, and n is a number selected from 1-3.

BACKGROUND OF THE INVENTION
The compounds of present invention are important intermediates in the pharmaceutical industry and find applications as intermediate in preparation of albaconazole, an antifungal and a neuroprotectant.
PCT Publication No. 1987007602 provides a process for preparation of 2-chloro-4-fluoro-5-nitrobenzoic acid by oxidising 2-chloro-4-fluorotoluene using potassium permanganate followed by nitration using nitric acid.
PCT Publication No. 2001083459 provides a process for preparation of 2-chloro-4-fluoro-5-nitrobenzoic acid from 2-chloro-4-fluorobenzoic acid using 90% nitric acid in presence of concentrated sulfuric acid.
The processes cannot be used commercially due to low yield and multiple operations steps.
Chinese Patent No. 106905161 provides a process for preparation of 2-chloro-4-fluoro-5-nitrobenzoic acid from 2-chloro-4-fluorobenzoic acid using concentrated sulfuric acid and fuming nitric acid in presence of cobalt chloride and zirconium chloride.
European Patent No. 1853548 provides a process for the preparation of 2-chloro-4-fluoro-5-nitrobenzoic acid by reacting 2-chloro-4-fluorobenzotrichloride with a sulfonitric mixture to give the intermediate 2-chloro-4-fluoro-5-nitrobenzotrichloride, which upon hydrolysis gives 2-chloro-4-fluoro-5-nitrobenzoic acid at high temperature. The hydrolysis is carried out using a Lewis acid catalyst, such as iron chloride and zinc chloride.
There is a need in the art to develop a process for preparation of compound of formula I without using metal catalyst, complex purification technique and adopting simple process conditions.
The present invention provides a process for preparation of compound of formula I without using any metal catalyst for nitration and hydrolysis process. The process not only avoids complex purification operations, but also provides good yield without compromising on product purity.

OBJECT OF THE INVENTION
The present invention provides an economical process for preparation of compound of formula I,

Formula I
wherein X is a halogen selected from Cl, F, Br and I, and n is a number selected from 1-3.

SUMMARY OF THE INVENTION
In first aspect, the present invention provides a process for preparation of a compound of formula I,

Formula I
wherein X is a halogen selected from Cl, F, Br and I, and n is a number selected from 1-3,
comprising the steps of:
i) chlorinating a compound of formula IV,

Formula IV
wherein X and n are as defined above,
with a chlorinating agent in presence of a light source and a catalyst to obtain a compound of formula III,

Formula III
wherein X and n are as defined above,
ii) hydrolysing the compound of formula III using an aqueous acid to obtain a compound of formula II, and

Formula II
wherein X and n are as defined above,
iii) nitrating the compound of formula II using nitrating agent to obtain the compound of formula I.

DETAILED DESCRIPTION OF THE INVENTION
In an embodiment, the compound of formula I is selected from 2-chloro-4-fluoro-5-nitrobenzoic acid; 2,6-dichloro-4-fluoro-5-nitrobenzoic acid and 2-chloro-6-bromo-4-fluoro-5-nitrobenzoic acid or the like.
In an embodiment, the compound of formula II is selected from 2-chloro-4-fluorobenzoic acid, 2,6-dichloro-4-fluorobenzoic acid and 2-chloro-6-bromo-4-fluorobenzoic acid or the like.
In an embodiment, the compound of formula III is selected from 2-chloro-4-fluorobenzotrichloride, 2,6-dichloro-4-fluorobenzotrichloride and 2-chloro-6-bromo-4-fluorobenzotrichloride or the like.
In an embodiment, the compound of formula IV is selected from 2-chloro-4-fluoro-1-methylbenzene, 2,6-dichloro-4-fluoro-1-methylbenzene, and 2-chloro-6-bromo-4-fluoro-1-methylbenzene or the like.
As used herein, organic solvent may be selected from dichloromethane, acetonitrile, acetone, dichloroethane, tetrahydrofuran, ethyl acetate, methyl acetate, tert-butyl methyl ether, diethyl ether, ethanol, and methanol or the like.
In an embodiment, present invention provides a chlorination of a compound of formula IV with a chlorinating agent in presence of light source and/or catalyst to obtain a compound of formula III.
In an embodiment, the light source is selected from a group consisting of visible light, UV lamp, sodium lamp and fluorescent tube lights or the like.
In an embodiment, the catalyst for chlorination is selected from a group consisting of azobisisobutyronitrile, azobisdimethylvaleronitrile, 2,2’-azobis-2-methyl butyronitrile, 1,1'-azobis(cyclohexanecarbonitrile), benzoyl peroxide and tert-butylhydroperoxide or the like.
In an embodiment, the light source of suitable wavelength from 300nm to 400nm at 225-260W.
The chlorinating agent is an elemental chlorine in a molar ratio in the range from 3-5 and preferably 3-3.5.
The catalyst is selected from chlorides such as phosphorous pentachloride, phosphorous trichloride, and silica gel supported phosphorus trichloride.
The molar ratio of catalyst with respect to compound of formula IV is in the range from 0.005-0.1.
After chlorination, reaction mass is flushed with an inert gas to remove gaseous content.
In an embodiment, the compound of formula III may further contain dichloromethyl side product and monochloromethyl side products.
In an embodiment, the compound of formula III is obtained with conversion of more than 99% and selectivity of more than 90%.
The crude reaction mass was directly rectified and the compound of formula III, is isolated with yield greater than 80%.
In an embodiment, the chlorination is carried out in absence of a solvent and generate no effluent in the process.
In an embodiment, the compound of formula III is hydrolysed using an aqueous acid selected from a group consisting of acetic acid, sulfuric acid, phosphoric acid, trifluoroacetic acid, chlorodifluoroacetic acid, trichloroacetic acid and conc. hydrochloric acid or a mixture thereof.
The hydrolysis is carried out a temperature selected from 50-120? and more preferably in 70-100?.
After hydrolysis, reaction mass is cooled to room temperature and extracted with an organic solvent to obtain the compound of formula II.
In an embodiment, the compound of formula II is isolated from reaction mass by solvent extraction.
In an embodiment, 2-chloro-4-fluorobenzotrichloride is hydrolysed using aqueous sulfuric acid and extracted with ethylacetate to obtain 2-chloro-4-fluorobenzoic acid, having purity>98% and yield> 80%.
In another embodiment, a compound of formula II is nitrated using a nitrating agent to obtain a compound of formula I.
As used herein, “nitrating agent” may be selected from a group consisting of nitric acid and nitrates such as potassium nitrate, sodium nitrate and copper nitrate, or the like.
In an embodiment, nitrating agent is used with an additional acid selected from glacial acetic acid, trichloroacetic acid, trifluoroacetic acid and phosphoric acid or concentrated sulfuric acid.
In preferred embodiment, the nitrating agent is 70% nitric acid or a mixture of concentrated nitric acid and concentrated sulfuric acid.
The nitration is carried out at a temperature selected in the range from 0-60?.
The molar ratio of nitrating agent to compound of formula III is in the range of 1-2, preferably 1.5.
In another embodiment, the present invention provides a process for preparation of a compound of formula I, wherein the process involves simultaneous hydrolysis and nitration of the compound of formula III using an acid to obtain a compound of formula I.
In another embodiment, the hydrolysis reaction mass was directly nitrated using a nitrating agent to obtain a compound of formula I.
In an embodiment, nitrating agent is selected from aqueous nitric acid and fuming nitric acid or a mixture of fuming nitric acid with concentrated sulfuric acid.
In an embodiment, the hydrolysis reaction mass is cooled to below 10? and dropwise added with a mixture of fuming nitric acid and concentrated sulfuric acid.
The nitrated reaction mass was gradually heated to 50-60? and maintained for 3-5 hours.
After nitration, quenched the reaction mass with water and extracted with an organic solvent.
In an embodiment, hydrolysed the 2-chloro-4-fluorobenzotrichloride using aqueous sulfuric acid and added fuming nitric acid to obtain 2-chloro-4-fluoro-5-nitrobenzoic acid, having purity>99% and yield> 70%.
In an embodiment, present invention provides a process for preparation of 2-chloro-4-fluoro-5-nitrobenzoic acid, comprising the steps of:
i) chlorinating 2-chloro-4-fluorotoluene with a chlorinating agent in presence of light source and catalyst to obtain 2-chloro-4-fluorobenzotrichloride;
ii) hydrolysing 2-chloro-4-fluorobenzotrichloride using an aqueous acid to obtain 2-chloro-4-fluorobenzoic acid; and
iii) nitrating 2-chloro-4-fluorobenzoic acid using an aqueous solution of nitrating agent to obtain 2-chloro-4-fluoro-5-nitrobenzoic acid.
In an embodiment, present invention provides a process for preparation of 2-chloro-4-fluoro-5-nitrobenzoic acid, comprising the steps of:
i) chlorinating 2-chloro-4-fluorotoluene with a chlorinating agent in presence of light source and a catalyst to obtain 2-chloro-4-fluorobenzotrichloride; and
ii) simultaneously hydrolysing and nitrating 2-chloro-4-fluorobenzotrichloride in presence of an acid to obtain 2-chloro-4-fluoro-5-nitrobenzoic acid.
In another embodiment, the present invention also provides a process for preparation of a compound of formula IV, comprising the steps of:
i) chlorinating a compound of formula VII

Formula VII
wherein X is a halogen selected from Cl, F, Br and I, and m is a number selected from 0 or 2,
with a chlorinating agent in presence of a catalyst to obtain a compound of formula VI;

Formula VI
wherein X is as defined above,
ii) hydrogenating the compound of formula VI in presence of catalyst to obtain a compound of formula V;

Formula V
wherein X is as defined above,
iii) diazotising the compound of formula V with a diazotising agent and decomposing to obtain a compound of formula IV;

Formula IV
wherein X is a halogen selected from Cl, F, Br and I, and n is a number selected from 1-3,
In an embodiment, the compound of formula V may be selected from 3-chloro-4-methylaniline, 3,5-dichloro-4-methylaniline and 3-bromo-4-methyl-5-chloroaniline or the like.
In an embodiment, the compound of formula VI may be 3-chloro-4-methylnitrobenzene, 3,5-dichloro-4-methynitrobenzene and 3-bromo-4-methyl-5-chloronitrobenzene or the like.
In an embodiment, the compound of formula VII may be 4-methylnitrobenzene, 3-chloro-4-methynitrobenzene and 3-bromo-4-methylnitrobenzene or the like.
In an embodiment, the compound of formula VII is chlorinated using a chlorinating agent and catalyst to obtain a compound of formula VI, wherein chlorinating agent is elemental chlorine.
In an embodiment, chlorination of compound of formula VII is carried out in presence of solvent. The solvent used is recycled in next batches and no effluent is generated.
In preferred embodiment, the catalyst for chlorination of compound of formula VII is iodine.
The compound of formula VI is isolated from chlorination reaction mass by distillation.
In an embodiment, 4-methylnitrobenzene is chlorinated using chlorine in catalytic presence of iodine and isolated 3-chloro-4-methylnitrobenzene, having purity> 98% and yield> 95%.
In an embodiment, the compound of formula VI is hydrogenated using hydrogen in presence of catalyst and a solvent.
The hydrogenation catalyst may be selected from a group consisting of Raney nickel, palladium, platinum, nickel oxide, lindlar catalyst and palladium on carbon or the like.
The solvent is an alcohol solvent selected from methanol, ethanol, propyl alcohol, isopropyl alcohol, butanol and tert-butanol or the like.
The molar ratio of solvent and hydrogenation catalyst is selected in the range from 10-15 and 0.001-0.01.
In an embodiment, hydrogen is continuously charged to the reactor at 60-100?.
In an embodiment, hydrogenation is carried out at a temperature in the range from 60-100?.
The hydrogenated product or compound of formula V is isolated from hydrogenation reaction mass by distillation.
In an embodiment, 3-chloro-4-methylnitrobenzene is hydrogenated using hydrogen in presence of raney nickel and methanol.
In an embodiment, the compound of formula V is isolated having purity> 98% and yield> 80%.
In an embodiment, the compound of formula V is diazotised using a diazotising agent to obtain a compound of formula IV.
The diazotising agent may be selected from a group consisting of nitrites such as sodium nitrites, potassium nitrites and nitrosyl sulfuric acid or the like.
The diazotisation is carried out in presence of an acid, preferably hydrogen fluoride.
The diazotisation is carried out at a temperature selected from 0-30?.
The diazotisation reaction is followed by decomposition process at 50-90?.
The decomposed reaction mass was separated into layers and organic layer is washed with a basic solution, isolated compound of formula IV by distillation.
In another embodiment, organic layer containing crude product of formula IV was neutralized using aqueous solution of potassium bicarbonate, sodium bicarbonate, sodium carbonate, potassium carbonate and potassium hydroxide or sodium hydroxide or so like.
In another embodiment, organic layer containing crude product of formula IV was neutralized most preferably using 8-10% potassium bicarbonate solution.
In an embodiment, 3-chloro-4-methylaniline is diazotised using sodium nitrite in presence of hydrogen fluoride and decomposed at 80? to isolate 2-chloro-4-fluoro-1-methylbenzne, having purity> 98% and yield> 90%.
In another embodiment, present invention also provides a process for preparation of 2-chloro-4-fluoro-1-methylbenzene, comprising the steps of:
i) chlorinating 4-methylnitrobenzene using chlorine in presence of catalytic iodine to obtain a 3-chloro-4-methylnitrobenzene;
ii) hydrogenating 3-chloro-4-methylnitrobenzene using hydrogen in presence of raney nickel in methanol to obtain 3-chloro-4-methylaniline; and
iii) diazotising 3-chloro-4-methylaniline with sodium nitrite and hydrogen fluoride and decomposing at 80? to obtain 2-chloro-4-fluoro-1-methylbenzene.
In an embodiment, present invention provides a process for preparation of a 2-chloro-4-fluoro-5-nitrobenzoic acid, comprising the steps of:
i) chlorinating 4-methylnitrobenzene using chlorine in presence of catalytic iodine to obtain a 3-chloro-4-methylnitrobenzene;
ii) hydrogenating 3-chloro-4-methylnitrobenzene using hydrogen in presence of raney nickel in methanol to obtain 3-chloro-4-methylaniline;
iii) diazotising 3-chloro-4-methylaniline with sodium nitrite and hydrogen fluoride and decomposing at 80? to obtain 2-chloro-4-fluoro-1-methylbenzene.
iv) chlorinating 2-chloro-4-fluoro-1-methylbenzene using chlorine in presence of UV lamp and phosphorous trichloride to obtain 2-chloro-4-fluorobenzotrichloride;
v) hydrolysing 2-chloro-4-fluorobenzotrichloride using aqueous sulfuric acid to obtain 2-chloro-4-fluorobenzoic acid; and
vi) nitrating 2-chloro-4- fluorobenzoic acid using an aqueous solution of nitric acid to obtain 2-chloro-4-fluoro-5-nitrobenzoic acid.
Unless stated to the contrary, any of the words “comprising”, “comprises” and includes mean “including without limitation” and shall not be construed to limit any general statement that it follows to the specific or similar items or matters immediately following it.
Embodiments of the invention are not mutually exclusive but may be implemented in various combinations. The described embodiments of the invention and the disclosed examples are given for the purpose of illustration rather than limitation of the invention as set forth in the appended claims.
The following example is given by way of illustration and therefore should not be construed to limit the scope of the present invention.
EXAMPLES
EXAMPLE 1: Preparation of 1-chloro-2-methyl-5-nitrobenzene
4-Nitrotoluene (50g, 0.36moles) and iodine (1wt.% w.r.t 4-nitro toluene) were charged into the reactor and purged chlorine gas (31g, 0.44moles) at 70-80? in the reactor. The progress of the reaction mass was monitored by gas chromatography. After achieving the desired conversion, cooled the reaction mass to 35-40oC and charged dichloromethane (100g, 1.2moles). The sodium bisulphite aqueous solution (10%, 3.6g, 0.035moles) was added to neutralise the reaction mixture. Separated the layers and isolated the titled compound by reducing the amount of solvent through evaporation. (Purity 98.3%, Yield 95%).
EXAMPLE 2: Preparation of 3-chloro-4-methylaniline
2-Chloro-4-nitrotoluene (50g, 0.29moles) in methanol (480g, 15.0moles) and 50% raney nickel (0.17g, 0.0015moles) were charged in 1000mL reactor under nitrogen atmosphere. The reaction mass was heated to 90? and pressure was raised to 16 bar by addition of hydrogen gas (1.75g, 0.88moles). The progress of the reaction was monitored by gas chromatography. After getting the desired conversion, cooled the reaction mass, unloaded under nitrogen atmosphere. The reaction mass was distilled out atmospherically to separate the solute, followed by negative pressure distillation to obtain pure 3-chloro-4-methylaniline (Purity 98.6, Yield 91.0%).
EXAMPLE 3: Preparation of 3-chloro-4-methylaniline
2-Chloro-4-nitrotoluene (50g, 0.29moles) in methanol (480g, 15.0moles) and 5% Pd/C (0.2g, 0.00005moles) were charged in 1000mL reactor under nitrogen atmosphere. The reaction mass was heated to 90? and pressure was raised to 16 bar by addition of hydrogen gas (1.75g, 0.88moles). The progress of the reaction was monitored by gas chromatography. After getting the desired conversion, cooled the reaction mass, unloaded under nitrogen atmosphere. The reaction mass was distilled out atmospherically to separate the solute, followed by negative pressure distillation to obtain pure 3-chloro-4-methylaniline (Purity 98.2, Yield 91.2%).
EXAMPLE 4: Preparation of 2-chloro-4-fluorotoluene
Hydrogen fluoride (74g, 3.71moles) was charged in a HAST-C reactor (250 mL) maintained at 0? and equipped with condenser. Charged 3-chloro-4-methylaniline (35g, 0.25moles) dropwise into reactor at 5 to 10?. Then, sodium nitrite (18g, 0.26 moles) was charged lotwise into the reaction mass while maintaining the temperature between 5 to 10? and gradually stirred at a temperature of 70-80oC for additional 2 hours. The reaction mass was cooled down to 5-10 ? and layers were separated. The organic layer was neutralized by using 8-10% aqueous potassium bicarbonate (388g, 0.35moles). The neutralized organic layer was distilled to get pure product 2-chloro-4-fluorotoluene (Purity >99.2, Yield : 80%).
EXAMPLE 5: Preparation of 2-chloro-4-fluorobenzotrichloride
2-Chloro-4-fluorotoluene (29g, 0.20 moles) and PCl3 catalyst (0.22g , 0.0016 moles) were charged in a photochemical reactor and purged chlorine gas (56.8g, 0.80 moles) into the reaction mass at 5-10? in the presence of light source (400nm, Voltage: 220V, Power: 250W). The progress of reaction was monitored by gas chromatography. After achieving the desired conversion, stopped chlorine purging. Then the reaction mass was flushed with nitrogen gas to expel the excess chlorine and reaction mass was vacuum rectified to isolate 2-chloro-4-fluorobenzotrichloride (Purity: > 99 %, Yield: 80%).
EXAMPLE 6: Preparation of 2-chloro-4-fluorobenzoic acid
Sulfuric acid (144g, 1.46moles) was charged into the reactor followed by added water (34.6g, 1.92moles) as dropwise into the mass between 25 and 50?. Then adjusted the reaction mass temperature to 70?. 2-chloro-4-fluorobenzotrichloride (39g, 0.16moles) was added as portion-wise into the reactor, then adjusted the mass temperature to 100-110 ?. Agitated the reaction mass at 110 ? for additional 3 hours. Progress of reaction was monitored by HPLC. After achieving the desired conversion, cooled to 50? and diluted with water (350g, 19.4moles). Then the product was extracted using ethyl acetate (140 g, 1.6moles) from the reaction mass and separated the layers. The obtained organic layer was washed with water (161g, 8.9moles) and concentrated to get 2-chloro-4-fluorobenzoic acid (Purity: 98.2%, Yield: 85%)
EXAMPLE 7: Preparation of 2-chloro-4-fluoro-5-nitrobenzoic acid
Sulfuric acid (218g, 2.20moles) and 2-chloro-4-fluorobenzoic acid (23g, 0.13moles) were added into the reactor and cooled the above reaction mixture to 0?. A mixture of fuming nitric acid (12.3 g, 0.19moles) and concentrated sulfuric acid (43.6g, 0.44moles) was added into the reaction mass as dropwise between 0-5?. The reaction mass was maintained at 0? for additional one hour. Then, heated to 50? and agitated for additional 3 hours. Progress of reaction is monitored by HPLC. After getting the desired conversion, Cooled the reaction mass to 25? and poured into ice water. Then the resultant was filtered to obtain white solid. The white solid was washed with water, dried at 60? for 8-10 h to obtain 2-chloro-4-fluoro-5-nitrobenzoic acid (Purity: 99.3%, Yield: 80%).
EXAMPLE 8: Preparation of 2-chloro-4-fluoro-5-nitrobenzoic acid (simultaneous hydrolysis and nitration)
Sulfuric acid (144g, 1.46moles) was charged into the reactor followed by added Water (34.6g, 1.92moles) as dropwise into the mass between 25 and 50? . Then adjusted the reaction mass temperature to 70?. 2-Chloro-4-fluorobenzotrichloride (39g, 0.16moles) was added as portion-wise into the reactor, then adjusted the mass temperature to 100-110 ? and agitated the reaction mass at 110 ? for additional 3 hours. The progress of reaction was monitored by HPLC. After achieving the desired conversion, cooled to 0? and slowly added sulfuric acid (75g, 0.76 moles). A mixture of fuming nitric acid (12.3 g, 0.19moles) and concentrated sulfuric acid (43.6g, 0.44moles) was added into the reaction mass as dropwise between 0-5?. The reaction mass was maintained at 0? for additional one hour. Then, heated to 50? and agitated for additional 3 hours. Progress of reaction is monitored by HPLC. After getting the desired conversion, Cooled the reaction mass to 25? and poured into ice water. Then the resultant was filtered to obtain white solid. The white solid was washed with water, dried at 60? for 8-10 hours to obtain 2-chloro-4-fluoro-5-nitrobenzoic acid (Purity: 99.1%, Yield: 70%).

,CLAIMS:WE CLAIM:
1. A process for preparation of a compound of formula I,

Formula I
wherein X is a halogen selected from Cl, F, Br and I, and n is a number selected from 1-3,
comprising the steps of:
i) chlorinating a compound of formula IV,

Formula IV
wherein X and n are as defined above,
with a chlorinating agent in presence of a light source and a catalyst to obtain a compound of formula III,

Formula III
wherein X and n are as defined above,
ii) hydrolysing the compound of formula III using an aqueous acid to obtain a compound of formula II, and

Formula II
wherein X and n are as defined above,
iii) nitrating the compound of formula II using nitrating agent to obtain the compound of formula I.
2. The process as claimed in claim 1, wherein the light source is selected from a group consisting of visible light, UV lamp, sodium lamp and fluorescent tube lights.
3. The process as claimed in claim 1, wherein the catalyst for chlorination is selected from a group consisting of azobisisobutyronitrile, azobisdimethylvaleronitrile, 2,2'-azobis-2-methyl butyronitrile, 1,1'-azobis(cyclohexanecarbonitrile), benzoyl peroxide, tert-butylhydroperoxide, phosphorous pentachloride, phosphorous trichloride, and silica gel supported phosphorus trichloride.
4. The process as claimed in claim 1, wherein the chlorination is carried out in absence of a solvent.
5. The process as claimed in claim 1, wherein the compound of formula III is hydrolysed using an aqueous acid selected from a group consisting of acetic acid, sulfuric acid, phosphoric acid, trifluoroacetic acid, chlorodifluoroacetic acid, trichloroacetic acid and conc. hydrochloric acid or a mixture thereof.
6. The process as claimed in claim 1, wherein the hydrolysis is carried out at a temperature selected from 50-120?.
7. The process as claimed in claim 1, wherein the nitrating agent is selected from a group consisting of nitric acid and nitrates selected from potassium nitrate, sodium nitrate and copper nitrate.
8. The process as claimed in claim 1, wherein the nitration is carried out at a temperature selected in the range from 0-60?.
9. The process as claimed in claim 1, wherein the process involves simultaneous hydrolysis and nitration of the compound of formula III using an acid to obtain the compound of formula I.

Dated this 20th day of December 2022.