DESC:“PREPARATION OF PYRIDINE-3-SULFONYL CHLORIDE”

FIELD OF THE INVENTION
The present invention relates to a process for the preparation of Pyridine-3-sulfonyl chloride with high yield and purity.

BACKGROUND OF THE INVENTION
Pyridine-3-sulfonyl chloride as a key intermediate for the preparation of potassium ion-competitive acid blocker (P-CAB), this intermediate is also used in the preparation of Vonoprazan, which is treated of gastroduodenal ulcer (including some drug-induced peptic ulcers) and reflux esophagitis.
Pyridine-3-sulfonyl chloride, is represented by structural Formula (I), which is a key intermediate for the preparation of Vonoprazan fumarate.

US 8048909 and US 7977488, discloses a process for the preparation of Pyridine-3-sulfonyl chloride of formula (I) by reacting pyridine-3-sulfonic acid of compound of formula (II) with phosphorus pentachloride and phosphorus oxychloride in presence of chloroform. The process is schematically shown as below:

US 9487485 discloses a process for the preparation of Pyridine-3-sulfonyl chloride of formula (I) by reacting pyridine-3-sulfonic acid of compound of formula (II) with phosphorus pentachloride in presence of chlorobenzene or trifluoromethylbenzene. The process is schematically shown as below:

Monthly books for chemistry, 1939, 72, 77-92, discloses a process for the preparation of pyridine-3-sulfonyl chloride of formula (I), which comprises pyridine of the formula (III) is treated with fuming sulfuric acid (Oleum) and Mercury(II) sulfate (HgSO4) (heavy metal) to obtain pyridine-3-sulfonic acid (II). The compound of the formula (II) is treated with phosphorus pentachloride (PCl5) to obtain Pyridine-3-sulfonyl chloride of formula (I). The process is schematically shown as below:

All the above processes disclose the preparation of the Pyridine-3-sulfonyl chloride by using chlorobenzene or trifluoromethylbenzene and chloroform solvents and Mercury(II) sulfate (HgSO4) (heavy metal) are difficult for bulk manufacturing process commercially.

Hence, there is consequently a need development for new methods to sort out prior art existing methods. So, our inventors have developed a method for the preparation of Pyridine-3-sulfonyl chloride by through free of heavy metal. The present invention is providing a simple, cost effective and industrial applicable process.

OBJECT OF THE INVENTION
The present invention relates to a process for the preparation of Pyridine-3-sulfonyl chloride (I) with high yield and purity.

SUMMARY OF THE INVENTION
The present invention provides a process for the preparation of Pyridine-3-sulfonyl chloride (I), comprising the steps of:
a) reacting pyridine (III) with sulfonating agent in presence of solvent or absence of solvent to obtain compound of formula (II), and

b) reacting compound of formula (II) with phosphorus chlorinating agent in presence of solvent or absence of solvent to obtain compound of formula (I)

DETAILED DESCRIPTION OF THE INVENTION
The present invention relates to a process for the preparation of Pyridine-3-sulfonyl chloride (I) with high yield and purity.

The present invention provides a process for the preparation of Pyridine-3-sulfonyl chloride (I), comprising the steps of:
a) reacting pyridine (III) with sulfonating agent in presence of solvent or absence of solvent to obtain compound of formula (II), and

b) reacting compound of formula (II) with phosphorus chlorinating agent in presence of solvent or absence of solvent to obtain compound of formula (I).

In an embodiment of the present invention, reacting pyridine (III) with sulfonating agent in presence of solvent or absence of solvent and the reaction is carried out at reflux temperature for 8-12 hours to obtain compound of formula (II).
According to an embodiment of the present invention, reacting compound of formula (II) with phosphorus chlorinating agent in presence of solvent or absence of solvent and the reaction is carried out at reflux temperature for 2-8 hours to obtain compound of formula (I).

According to an embodiment of the present invention provides Pyridine-3-sulfonyl chloride (I) having HPLC purity = 99.0%.

According to an embodiment of the present invention, wherein the sulfonating agent is selected from, fuming sulfuric acid (Oleum), sulfuric acid, sulfur trioxide (SO3), chlorosulfuric acid and fluorosulfuric acid or mixtures thereof.

According to an embodiment of the present invention, wherein the phosphorus chlorinating agent is selected from, phosphorus pentachloride, phosphorus oxychloride and phosphorus trichloride or mixtures thereof.

According to an embodiment of the present invention. wherein the solvent is selected from tetrahydrofuran, toluene, water, acetone, acetonitrile, ethyl acetate, isopropyl alcohol, methanol, ethanol, dimethyl sulfoxide (DMSO), dimethylformamide (DMF), isopropyl acetate and n-butyl acetate, methyl ethyl ketone, methyl isobutyl ketone, cyclohexanone, n-hexane, diethyl ether, diisopropyl ether, dioxane, 1,2-dimethoxyethane, dichloromethane (MDC), dichloroethane, ethylene dichloride (1,2-dichloroethane), carbon tetrachloride and chloroform, methyl tert-butyl ether (MTBE), N-methyl-2-pyrrolidone (NMP), 2-methoxy ethanol, dimethoxyethane, glycol diethyl ether, ethylene glycol ethyl ether or ethylene glycol, and/or mixtures thereof.

The following examples illustrate the present invention, but should not be construed as limiting the scope of the invention.

EXAMPLES
Example-1:
Preparation of Pyridine-3-sulfonic acid (II)
Concentrated sulfuric acid (125gr) and pyridine (100gr) were added into round bottom flask (RBF) and stir for 18-20 hours at 300° to 350°C. The obtain reaction mixture was cooled to room temperature and add ethyl acetate (500ml) and water (500ml). The product obtained by distilled solvent and dry the materials to give the title compound as a solid.
Yield: 85% (172gr).
Purity: 95.0%

Example-2:
Preparation of Pyridine-3-sulfonic acid (II)
Fuming sulfuric acid (228gr) into round bottom flask (RBF), followed by dropwise add pyridine (100gr) at 260°C to 280°C. The reaction mass maintained for 10-12 hrs at same temperature. After completion of the reaction, the reaction mas was cooled to room temperature. The obtained reaction mass was recrystallized with ethyl acetate (200ml) to obtained product, dry the materials to give the title compound as a solid.
Yield: 84% (170gr).
Purity: 95.0%

Example-3:
Preparation of Pyridine-3-sulfonyl chloride (I)
Phosphorus pentachloride (80gr), Phosphorus oxychloride (50gr) and Pyridine-3-sulfonic acid (50gr) were suspended in dichloromethane (500ml) at room temperature. The reaction mass was allowing to 105±5°C for 2 hr, the mixture was cooled to room temperature, followed by add water (500ml) and separate the two layers. The obtained precipitated crystals were collected by filtration and washed with dichloromethane (80ml) to give the title compound.
Yield: 80 % (45gr).
Purity: 99.5%.

Example-4:
Preparation of Pyridine-3-sulfonyl chloride (I)
Phosphorus pentachloride (106gr) and Pyridine-3-sulfonic acid (80gr) were suspended in 1,2-dichloroethane (600ml) at room temperature. The reaction mass was allowing to 120±5°C for 4 hr, the mixture was cooled to room temperature and obtained precipitated crystals were collected by filtration and washed with 1,2-dichloroethane (400ml) to give the title compound.
Yield: 77 % (69 gr).
Purity: 99.6 %.

Example-5:
Preparation of Pyridine-3-sulfonyl chloride (I)
Phosphorus pentachloride (105gr) and Pyridine-3-sulfonic acid (80gr) were added into round bottom flask (RBF) and stirring under reflux temperature for 4 hours. The obtained reaction mixture was cooled to room temperature and obtained precipitated crystals were collected by filtration and crystallized with 1,2-dichloroethane (400ml) to give the title compound.
Yield: 80 % (72 gr).
Purity: 99.6 %.

Example-6:
Preparation of Pyridine-3-sulfonyl chloride (I)
Phosphorus pentachloride (80gr), Phosphorus oxychloride (55gr) and Pyridine-3-sulfonic acid (50gr) were suspended into round bottom flask (RBF) at room temperature. The reaction mass was allowing reflux temperature. After completion of the reaction, the reaction mas was cooled to room temperature. Distil off the excessive Phosphorus pentachloride. The obtained residue into ice water to cool down, followed by adjust pH with sodium bicarbonate. The resultant reaction mass extract with dichloromethane (800ml), dry organic phase with anhydrous magnesium sulphate and concentrate to distil off dichloromethane. The obtained product was distilled out to obtained the title of the compound.
Yield: 78 % (44gr).
Purity: 99.6 %.

Example-7:
Preparation of Pyridine-3-sulfonyl chloride (I)
Pyridine-3-sulfonic acid (80gr), phosphorus pentachloride (105gr) and dichloromethane (650ml) were added into round bottom flask (RBF) at room temperature. After stirring under reflux temperature, the mixture was cooled to room temperature, followed by add Phosphorus oxychloride (80gr) and stir for under reflux temperature. After completion of the reaction, the reaction mas added with water (500ml) and dichloromethane (600ml). The obtained mass was extraction and separation, distilled out. The obtained product purification with dichloromethane (250ml) to obtain the title product.
Yield: 79 % (71gr).
Purity: 99.6 %.
,CLAIMS:We Claim:
1. A process for the preparation of Pyridine-3-sulfonyl chloride (I), comprising the steps of:
a) reacting pyridine (III) with sulfonating agent in presence of solvent or absence of solvent to obtain compound of formula (II), and

b) reacting compound of formula (II) with phosphorus chlorinating agent in presence of solvent or absence of solvent to obtain compound of formula (I).

2. The process as claimed in claim 1, wherein the sulfonating agent is selected from, fuming sulfuric acid (Oleum), sulfuric acid, sulfur trioxide (SO3), chlorosulfuric acid and fluorosulfuric acid or mixtures thereof.

3. The process as claimed in claim 1, wherein the phosphorus chlorinating agent is selected from, phosphorus pentachloride, phosphorus oxychloride and phosphorus trichloride or mixtures thereof.

4. The process as claimed in claim 1, wherein the solvent is selected from tetrahydrofuran, toluene, water, acetone, acetonitrile, ethyl acetate, isopropyl alcohol, methanol, ethanol, dimethyl sulfoxide (DMSO), dimethylformamide (DMF), isopropyl acetate and n-butyl acetate, methyl ethyl ketone, methyl isobutyl ketone, cyclohexanone, n-hexane, diethyl ether, diisopropyl ether, dioxane, 1,2-dimethoxyethane, dichloromethane (MDC), dichloroethane, ethylene dichloride (1,2-dichloroethane), carbon tetrachloride and chloroform, methyl tert-butyl ether (MTBE), N-methyl-2-pyrrolidone (NMP), 2-methoxy ethanol, dimethoxyethane, glycol diethyl ether, ethylene glycol ethyl ether or ethylene glycol, and/or mixtures thereof.