118175-10-3

Basic information

• Product Name: 2-Hydroxymethyl-3-methyl-4-(3-methoxy propanoxyl)pyridine
• Synonyms: 2-Hydroxymethyl-3-methyl-4-(3-methoxy propanoxyl)pyridine;2-(Hydroxymethyl)-4-(3-methoxypropoxy)--picoline;4-[3-MethoxyPropoxy]-3-Methyl-2-HydroxymethylPyridineHcl;2-Hydroxymethyl-4-(3-methoxypropoxy)-3-methylpyridineHCl;4-(3-METHOXYPROPOXY)-3-METHYL-2-PYRIDYL]METHANOL;4-(3-Methoxypropoxy)-3-methyl-2-hydroxymethyl pyridine;3-METHYL 4-(3-METHOXY PROPOXY) 2-HYDROXYMETHYL PYRIDINE;2-Hydroxymethyl-4-(3-methoxypropoxy)-3-methylpyridine
• CAS NO: 118175-10-3
• Molecular Formula: C₁₁H₁₇NO₃
• Molecular Weight: 211.26
• EINECS: 1592732-453-0
• Product Categories: PHARMACEUTICAL INTERMEDIATES;API intermediates;Heterocycle-Pyridine series
• Mol File: 118175-10-3.mol
• Article Data: 4

Chemical Properties

• Boiling Point: 342.808 °C at 760 mmHg
• Flash Point: 161.125 °C
• Appearance: /
• Density: 1.097 g/cm³
• Storage Temp.: Inert atmosphere,Room Temperature
• PKA: 13.21±0.10(Predicted)
• CAS DataBase Reference: 2-Hydroxymethyl-3-methyl-4-(3-methoxy propanoxyl)pyridine(CAS DataBase Reference)
• NIST Chemistry Reference: 2-Hydroxymethyl-3-methyl-4-(3-methoxy propanoxyl)pyridine(118175-10-3)
• EPA Substance Registry System: 2-Hydroxymethyl-3-methyl-4-(3-methoxy propanoxyl)pyridine(118175-10-3)

Safety Data

• Statements: 36/37/38
• Safety Statements: 26-36
• Hazardous Substances Data: 118175-10-3(Hazardous Substances Data)

Usage

Description

2-Hydroxymethyl-3-methyl-4-(3-methoxy propanoxyl)pyridine is an organic compound characterized by its colorless liquid state. It is a specific type of pyridine derivative with a unique structure that includes a hydroxymethyl group, a methyl group, and a methoxy propanoxyl group attached to its pyridine ring. 2-Hydroxymethyl-3-methyl-4-(3-methoxy propanoxyl)pyridine serves as a crucial intermediate in the synthesis of various pharmaceutical compounds.

Uses

Used in Pharmaceutical Industry:
2-Hydroxymethyl-3-methyl-4-(3-methoxy propanoxyl)pyridine is used as an intermediate for the synthesis of various benzimidazoles, benzothiazoles, and benzoxazoles derivatives. These derivatives are known for their ulcer-inhibiting properties, making this compound a valuable asset in the development of medications aimed at treating ulcers and related gastrointestinal disorders.
Used in Chemical Synthesis:
As a versatile intermediate, 2-Hydroxymethyl-3-methyl-4-(3-methoxy propanoxyl)pyridine can be utilized in the chemical synthesis of a wide range of compounds beyond those with pharmaceutical applications. Its unique structure allows for further functionalization and modification, making it a potentially useful building block in the creation of new molecules for various industries, including materials science, agrochemicals, and more.

InChI:InChI=1/C11H17NO3.ClH/c1-9-10(8-13)12-5-4-11(9)15-7-3-6-14-2;/h4-5,13H,3,6-8H2,1-2H3;1H

Synthetic route

2-acetoxymethyl-4-(3-methoxy propoxy)-3-methyl pyridine → 2-hydroxymethyl-4-(3-methoxy propoxy)-3-methyl pyridine (118175-10-3)

Conditions	Yield
With water; sodium hydroxide at 80℃; for 1h; pH=14;	92.1%
With sodium hydroxide; water at 20 - 50℃; for 1h;
With sodium hydroxide In ethanol at 20 - 55℃;
With ethanol; sodium hydroxide at 20 - 55℃; for 2h; Inert atmosphere;	98 g

2,3-dimethyl-4-(3-methoxypropoxy)pyridine nitroxide (117977-18-1) → 2-hydroxymethyl-4-(3-methoxy propoxy)-3-methyl pyridine (118175-10-3)

Conditions	Yield
Multi-step reaction with 2 steps 1: 6.5 h / 0 - 90 °C / Inert atmosphere 2: sodium hydroxide; ethanol / 2 h / 20 - 55 °C / Inert atmosphere View Scheme
Multi-step reaction with 2 steps 1: toluene-4-sulfonic acid / 3 h / 50 °C 2: sodium hydroxide; water / 1 h / 80 °C / pH 14 View Scheme

2-hydroxymethyl-4-(3-methoxy propoxy)-3-methyl pyridine (118175-10-3) → 2-chloromethyl-4-(3-methoxy propyloxy)-3-methyl pyridine (117977-20-5)

Conditions	Yield
With thionyl chloride In dichloromethane at 20 - 25℃; Product distribution / selectivity;	99%
With thionyl chloride In 1,2-dimethoxyethane at 20 - 25℃; Product distribution / selectivity;	99.2%
Stage #1: 2-hydroxymethyl-4-(3-methoxy propoxy)-3-methyl pyridine With thionyl chloride In dichloromethane at 0 - 20℃; Stage #2: With sodium hydrogencarbonate In water at 5℃; pH=7.5;	99%

2-hydroxymethyl-4-(3-methoxy propoxy)-3-methyl pyridine (118175-10-3) → Reaxys ID: 11530903

Conditions	Yield
With thionyl chloride In dichloromethane at 20 - 25℃; Product distribution / selectivity;	99%
With thionyl chloride In 1,2-dimethoxyethane at 20 - 25℃; Product distribution / selectivity;	99.2%
With thionyl chloride In toluene at 20 - 25℃; Product distribution / selectivity;	97.3%
With thionyl chloride In ethyl acetate at 20 - 25℃; Product distribution / selectivity;	97.4%

2-hydroxymethyl-4-(3-methoxy propoxy)-3-methyl pyridine (118175-10-3) → 2-chloromethyl-4-(3-methoxypropoxy)-3-methylpyridine hydrochloride

Conditions	Yield
With thionyl chloride In ethyl acetate at 5 - 20℃; for 3h; Temperature;	95.7%

2-hydroxymethyl-4-(3-methoxy propoxy)-3-methyl pyridine (118175-10-3) + Benzimidazol-2-thiol (134469-07-1) → rabeprazole sulfide (117977-21-6)

Conditions	Yield
With triphenylphosphine; diethylazodicarboxylate In tetrahydrofuran at 0 - 10℃; Mitsunobu Displacement;	80%

2-hydroxymethyl-4-(3-methoxy propoxy)-3-methyl pyridine (118175-10-3) → rabeprazole (117976-89-3)

Conditions	Yield
Multi-step reaction with 2 steps 1: triphenylphosphine; diethylazodicarboxylate / tetrahydrofuran / 0 - 10 °C 2: sodium hydroxide; sodium hypochlorite / acetonitrile; water / 2 h / 0 - 5 °C View Scheme

2-hydroxymethyl-4-(3-methoxy propoxy)-3-methyl pyridine (118175-10-3) → Rabeprazole sodium (117976-90-6)

Conditions	Yield
Multi-step reaction with 3 steps 1: triphenylphosphine; diethylazodicarboxylate / tetrahydrofuran / 0 - 10 °C 2: sodium hydroxide; sodium hypochlorite / acetonitrile; water / 2 h / 0 - 5 °C 3: sodium hydroxide / methanol / 1 h / 20 °C View Scheme

2-hydroxymethyl-4-(3-methoxy propoxy)-3-methyl pyridine (118175-10-3) → rabeprazole sulfide (117977-21-6)

Conditions	Yield
Multi-step reaction with 2 steps 1: thionyl chloride / dichloromethane / 2 h / 0 - 20 °C / Inert atmosphere 2: sodium hydroxide; ethanol / 2 h / 55 °C / Inert atmosphere View Scheme

2-hydroxymethyl-4-(3-methoxy propoxy)-3-methyl pyridine (118175-10-3) → 5-(difluoromethoxy)-2-(((4-(3-methoxypropoxy)-3-methylpyridin-2-yl)methyl)sulfinyl)-1H-benzo[d]imidazole

Conditions	Yield
Multi-step reaction with 3 steps 1: thionyl chloride / dichloromethane / 2 h / 20 °C 2: sodium hydroxide / methanol / 0.5 h / 20 °C 3: sodium hydroxide; sodium hypochlorite / ethyl acetate; water / 20 °C View Scheme

2-hydroxymethyl-4-(3-methoxy propoxy)-3-methyl pyridine (118175-10-3) → 5-(difluoromethoxy)-2-(((4-(3-methoxypropoxy)-3-methylpyridin-2-yl)methyl)sulfonyl)-1H-benzo[d]imidazole

Conditions	Yield
Multi-step reaction with 4 steps 1: thionyl chloride / dichloromethane / 2 h / 20 °C 2: sodium hydroxide / methanol / 0.5 h / 20 °C 3: sodium hydroxide; sodium hypochlorite / ethyl acetate; water / 20 °C 4: sodium hydrogencarbonate; 3-chloro-benzenecarboperoxoic acid / dichloromethane / 20 °C View Scheme

2-hydroxymethyl-4-(3-methoxy propoxy)-3-methyl pyridine (118175-10-3) → 2-{[4-(3-methoxy-propoxy)-3-methylpyridine-2-yl]-methylthio}-1H-5-difluoromethoxyl-benzimidazole

Conditions	Yield
Multi-step reaction with 2 steps 1: thionyl chloride / dichloromethane / 2 h / 20 °C 2: sodium hydroxide / methanol / 0.5 h / 20 °C View Scheme

Upstream product

• 117977-18-1 2,3-dimethyl-4-(3-methoxypropoxy)pyridine nitroxide 

Downstream Products

• 117976-89-3 rabeprazole 
• 117976-90-6 Rabeprazole sodium 
• 117977-21-6 rabeprazole sulfide 
• 117977-20-5 2-chloromethyl-4-(3-methoxy propyloxy)-3-methyl pyridine 

Relevant articles and documents

Preparation method of rabeprazole chloride and intermediate thereof

According to an existing method, acetic anhydride is adopted for a reaction when a formula III is synthesized from a formula IV, the reaction temperature is high, the reaction time is long, a large number of isomer byproducts can be generated in the reaction process, and the product purity is low. When the compound shown in the formula I is synthesized from free alkali of a compound shown in a formula II, halogenated alkane is used as a solvent and thionyl chloride is used as a chlorination reagent for reaction, alkali quenching, water washing extraction and salt formation after concentrationare needed for aftertreatment, the operation is complex, and the production period is long. According to the invention, p-toluenesulfonic acid is added for catalysis when the compound shown as the formula III is prepared, so that the reaction can be carried out at a relatively low temperature, the side reaction is greatly reduced, and the purity of the product is improved. When the compound shownin the formula I is prepared, ethyl acetate is used as a solvent, a product is gradually separated out along with the reaction, the product can be obtained through direct filtration after the reactionis completed, aftertreatment is simple, the product purity is high, and the method is suitable for industrial production.

PROCESS FOR PREPARATION OF PYRIDINYLMETHYLSULPHINYL BENZIMIDAZOLE COMPOUNDS AND PYRIDINE INTERMEDIATES

Process for preparing 4-chloro-substituted pyridine intermediates of Formula (I), useful for preparation of pyridinylmethylsulphinyl benzimidazole compounds, especially Rabeprazole is disclosed herein. The invention, further describes process for preparation of stable Rabeprazole sodium of high purity in a reproducible and consistent manner.