50390-76-6

Basic information

• Product Name: 2-Methoxy-5-(methylsulfonyl)benzoic acid
• Synonyms: 5-METHANESULFONYL-2-METHOXY-BENZOIC ACID;2-METHOXY-5-METHYL SULFONYLBENZOIC ACID;4-methox+c578y-3-carboxymethylbenzenesulponate;5-mesyl-o-anisic acid;2-methoxyl-5-methysulfonyl benzoic acid;2-Methoxy-5-methy1 sulfonylbenzoic acid;2-Methoxy-5-(methylsulphonyl)benzoic acid;2-METHOXY-6-(METHYLSULPHONYL)BENZOIC ACID
• CAS NO: 50390-76-6
• Molecular Formula: C₉H₁₀O₅S
• Molecular Weight: 230.24
• EINECS: 256-573-4
• Product Categories: (intermmediate of tiapride hcl)
• Mol File: 50390-76-6.mol
• Article Data: 5

Chemical Properties

• Melting Point: 190 °C
• Boiling Point: 467.9oC at 760 mmHg
• Flash Point: 236.8oC
• Appearance: /
• Density: 1.372g/cm3
• Vapor Pressure: 1.48E-09mmHg at 25°C
• Refractive Index: 1.542
• Storage Temp.: Sealed in dry,Room Temperature
• Solubility: DMSO (Slightly), Methanol (Slightly, Heated)
• PKA: 3.49±0.10(Predicted)
• CAS DataBase Reference: 2-Methoxy-5-(methylsulfonyl)benzoic acid(CAS DataBase Reference)
• NIST Chemistry Reference: 2-Methoxy-5-(methylsulfonyl)benzoic acid(50390-76-6)
• EPA Substance Registry System: 2-Methoxy-5-(methylsulfonyl)benzoic acid(50390-76-6)

Safety Data

• Hazard Codes: Xi
• Hazardous Substances Data: 50390-76-6(Hazardous Substances Data)

Usage

General Description

2-Methoxy-5-(methylsulfonyl)benzoic acid is a chemical organic compound with the molecular formula C9H10O5S. This substance belongs to the family of Methoxybenzoic Acids and derivatives which are compounds containing a methoxybenzoic acid moiety (or a derivative thereof), which is a benzoic acid in which one of the hydrogen atoms of the benzene ring is replaced by a methoxy group. Known for its acid characteristics, it's generally used in the field of organic synthesis, preparing medicines, dyes, and pesticides. However, detailed information about its physical properties, toxicity, handling precautions and environmental impact may vary and should be referred to from specific Material Safety Data Sheet(MSDS) based on suppliers' production and version.

InChI:InChI=1/C9H10O5S/c1-14-8-4-3-6(15(2,12)13)5-7(8)9(10)11/h3-5H,1-2H3,(H,10,11)

Synthetic route

1-methoxy-2-methyl-4-(methylthio)benzene (50390-78-8) → 2-methoxy-5-methylsulphonylbenzoic acid (50390-76-6)

Conditions	Yield
With potassium permanganate; potassium carbonate

2-methoxy-5-(methylthio)benzoic acid (61694-97-1) → 2-methoxy-5-methylsulphonylbenzoic acid (50390-76-6)

Conditions	Yield
With potassium permanganate; potassium carbonate

5-chlorosulfonyl-2-anisic acid (51904-91-7) + chloroacetic acid (79-11-8) → 2-methoxy-5-methylsulphonylbenzoic acid (50390-76-6)

Conditions	Yield
With sodium hydroxide; sodium hydrogencarbonate; sodium sulfite 1) H2O, 75 deg C, 1 h, 2) 105 deg C, 47 h; Yield given. Multistep reaction;

1-methoxy-2-methyl-4-(methylthio)benzene (50390-78-8) + KMnO4 + aqueous K2CO3 → 2-methoxy-5-methylsulphonylbenzoic acid (50390-76-6)

4-methoxy-3-methylbenzenethiol (698-32-8) → 2-methoxy-5-methylsulphonylbenzoic acid (50390-76-6)

Conditions	Yield
Multi-step reaction with 2 steps 1: aqueous NaOH 2: potassium carbonate; aqueous potassium permanganate solution View Scheme

5-chlorosulfonyl-2-anisic acid (51904-91-7) → 2-methoxy-5-methylsulphonylbenzoic acid (50390-76-6)

Conditions	Yield
Multi-step reaction with 3 steps 1: tin; aqueous hydrochloric acid 2: aq. NaOH solution 3: potassium carbonate; aqueous potassium permanganate solution View Scheme

5-mercapto-2-methoxybenzoic acid (80530-56-9) → 2-methoxy-5-methylsulphonylbenzoic acid (50390-76-6)

Conditions	Yield
Multi-step reaction with 2 steps 1: aq. NaOH solution 2: potassium carbonate; aqueous potassium permanganate solution View Scheme

4-methoxy-3-methylbenzene-1-sulfonyl chloride (84910-98-5) → 2-methoxy-5-methylsulphonylbenzoic acid (50390-76-6)

Conditions	Yield
Multi-step reaction with 3 steps 1: tin; aqueous HCl / zuletzt auf dem Dampfbad 2: aqueous NaOH 3: potassium carbonate; aqueous potassium permanganate solution View Scheme

aqueous potassium hydroxide + methyl 2-(methyloxy)-5-(methylsulfonyl)benzoate → 2-methoxy-5-methylsulphonylbenzoic acid (50390-76-6)

Conditions	Yield
With hydrogenchloride
With hydrogenchloride
With hydrogenchloride
With hydrogenchloride

2-methoxy-5-methylsulphonylbenzoic acid (50390-76-6) + (E)-methyl 4-aminobut-2-enoate trifluoroacetic acid salt (99281-88-6) → (E)-methyl 4-(2-methoxy-5-(methylsulfonyl)benzamido)but-2-enoate

Conditions	Yield
With N-ethyl-N,N-diisopropylamine; N-[(dimethylamino)-3-oxo-1H-1,2,3-triazolo[4,5-b]pyridin-1-yl-methylene]-N-methylmethanaminium hexafluorophosphate In N,N-dimethyl-formamide at 20℃; Sealed tube;	74%

7β-amino-9-benzyl-9-aza-3-thiabicyclo[3.3.1]nonane + 2-methoxy-5-methylsulphonylbenzoic acid (50390-76-6) + chloroformic acid ethyl ester (541-41-3) → 2-methoxy-5-methylsulphonyl-N-[9-benzyl-9-aza-3-thiabicyclo(3,3,1)nonan-7β-yl]benzamide

Conditions	Yield
With triethylamine In N-methyl-acetamide	70%

3-fluoro-4-piperazin-1-yl-benzonitrile hydrochloride + 2-methoxy-5-methylsulphonylbenzoic acid (50390-76-6) → 3-fluoro-4-[4-(5-methanesulfonyl-2-methoxy-benzoyl)-piperazin-1-yl]-benzonitrile (1229627-87-5)

Conditions	Yield
With O-(benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborate; N-ethyl-N,N-diisopropylamine In N,N-dimethyl-formamide at 20℃;	69%

2-methoxy-5-methylsulphonylbenzoic acid (50390-76-6) + chloroformic acid ethyl ester (541-41-3) → C12H14O7S (94134-08-4)

Conditions	Yield
With triethylamine In dichloromethane at -40 - -10℃; for 0.5h;

2-methoxy-5-methylsulphonylbenzoic acid (50390-76-6) → N-[2-(N'-benzyl-N'-methylamino)ethyl]-6-methoxy-3-methylsulfonylbenzamide (61694-34-6)

Conditions	Yield
Multi-step reaction with 2 steps 1: triethylamine / CH2Cl2 / 0.5 h / -40 - -10 °C 2: CH2Cl2 / 2 h / Ambient temperature View Scheme

3-(pyridin-2-yl)-1H-pyrazol-4-amine (896467-81-5) + 2-methoxy-5-methylsulphonylbenzoic acid (50390-76-6) → 5-methanesulfonyl-2-methoxy-N-(3-pyridin-2-yl-1H-pyrazol-4-yl)benzamide

Conditions	Yield
With 1-hydroxy-7-aza-benzotriazole; N-(3-dimethylaminopropyl)-N-ethylcarbodiimide In N,N-dimethyl-formamide at 20℃; for 2h;

3-(2-(4-(1-(2-ethoxyethyl)-1H-benzimidazol-2-yl)[1,4]diazepan-1-yl)ethyl)-3-phenylpyrrolidine hydrochloric acid salt (192940-77-5) + (+)-3-phenyl-3-(2-hydroxy-ethyl)-pyrrolidine (R,R)-di-p-anisoyltartaric acid salt (1133464-33-1, 178371-24-9, 178371-26-1) + 2-methoxy-5-methylsulphonylbenzoic acid (50390-76-6) → 1-(2-methoxy-5-methylsulfonylbenzoyl)-3-(2-(4-(1-(2-ethoxyethyl)-1H-benzimidazol-2-yl)[1,4]diazepan-1-yl)ethyl)-3-phenylpyrrolidine

2-methoxy-5-methylsulphonylbenzoic acid (50390-76-6) + chloroformic acid ethyl ester (541-41-3) + 4-Amino-1,2-diethyl-pyrazolidine (70180-92-6) → N-(1.2-Diethyl-4-pyrazolidinyl)-2-methoxy-5-(methylsulfonyl)-benzamide

Conditions	Yield
With triethylamine In dichloromethane	1.03 g (29%)

1-norbornyl-2-aminomethyl pyrrolidine + 2-methoxy-5-methylsulphonylbenzoic acid (50390-76-6) + isobutyl chloroformate (543-27-1) → N-(1-norbornyl-2-pyrrolidylmethyl)-2-methoxy-5-methylsulphonyl benzamide

Conditions	Yield
With hydrogenchloride; triethylamine In water; ethyl acetate; isopropyl alcohol; acetone

1,4-dioxane (123-91-1) + 4-methyl 2-chloro 1-3-2-dioxophosphorinane + 2-methoxy-5-methylsulphonylbenzoic acid (50390-76-6) + N,N-diethylethylenediamine (100-36-7) → tiapride (51012-32-9)

Conditions	Yield
In water

2-methoxy-5-methylsulphonylbenzoic acid (50390-76-6) + N-benzyl-N-methylethylenediamine (14165-18-5) → N-[2-(N'-benzyl-N'-methylamino)ethyl]-6-methoxy-3-methylsulfonylbenzamide (61694-34-6)

(-)-3-phenyl-3-(2-hydroxyethyl)pyrrolidine(R,R)-di-p-anisoyltartaric acid salt + 3-(2-(4-(1-(2-ethoxyethyl)-1H-benzimidazol-2-yl)[1,4]diazepan-1-yl)ethyl)-3-phenylpyrrolidine hydrochloric acid salt (192940-77-5) + 2-methoxy-5-methylsulphonylbenzoic acid (50390-76-6) → 1-(2-methoxy-5-methylsulfonylbenzoyl)-3-(2-(4-(1-(2-ethoxyethyl)-1H-benzimidazol-2-yl)[1,4]diazepan-1-yl)ethyl)-3-phenylpyrrolidine

(+)-3-phenyl-3-(2-hydroxy-ethyl)-pyrrolidine (R,R)-di-p-anisoyltartaric acid salt (1133464-33-1, 178371-24-9, 178371-26-1) + 3-(2-(4-(1-(2-ethoxyethyl)-1H-benzimidazol-2-yl-amino)piperidin-1-yl)ethyl)-3-phenylpyrrolidine hydrochloric acid salt + 2-methoxy-5-methylsulphonylbenzoic acid (50390-76-6) → 1-(2-methoxy-5-methylsulfonylbenzoyl)-3-(2-(4-(1-(2-ethoxyethyl)-1H-benzimidazol-2-yl-amino)piperidin-1-yl)ethyl)-3-phenylpyrrolidine

2-methoxy-5-methylsulphonylbenzoic acid (50390-76-6) → C2HF3O2*C15H24N2O4S3 (1297600-41-9)

Conditions	Yield
Multi-step reaction with 2 steps 1: benzotriazol-1-ol; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride / water; N,N-dimethyl-formamide 2: tris-(2-carboxyethyl)-phosphine hydrochloride; triethylamine / water; N,N-dimethyl-formamide View Scheme

2-methoxy-5-methylsulphonylbenzoic acid (50390-76-6) + cystamine dihydrochioride (56-17-7) → C22H28N2O8S4

Conditions	Yield
With benzotriazol-1-ol; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride In water; N,N-dimethyl-formamide

2-methoxy-5-methylsulphonylbenzoic acid (50390-76-6) → 2-chloro-N-(2-methoxy-5-(methylsulfonyl)benzyl)-5-methylpyrimidin-4-amine

Conditions	Yield
Multi-step reaction with 3 steps 1: borane-THF / tetrahydrofuran / 16 h / 0 °C 2: phosphorus tribromide / dichloromethane / 18 h / 20 °C 3: potassium carbonate / acetonitrile / 100 °C View Scheme

2-methoxy-5-methylsulphonylbenzoic acid (50390-76-6) → 2-(bromomethyl)-1-methoxy-4-(methylsulfonyl)benzene (294860-49-4)

Conditions	Yield
Multi-step reaction with 2 steps 1: borane-THF / tetrahydrofuran / 16 h / 0 °C 2: phosphorus tribromide / dichloromethane / 18 h / 20 °C View Scheme

2-methoxy-5-methylsulphonylbenzoic acid (50390-76-6) → (2-methoxy-5-(methylsulfonyl)phenyl)methanol

Conditions	Yield
With borane-THF In tetrahydrofuran at 0℃; for 16h;	4.9 g

2-methoxy-5-methylsulphonylbenzoic acid (50390-76-6) → 2-(2-methoxy-5-(methylsulfonyl)phenyl)oxazole

Conditions	Yield
Multi-step reaction with 4 steps 1: thionyl chloride / 3 h / Reflux; Inert atmosphere 2: triethylamine / dichloromethane / 20 °C 3: hydrogenchloride / acetone; water / 5 h / Reflux 4: Burgess Reagent / tetrahydrofuran / 0.17 h / 70 °C / Microwave irradiation View Scheme

2-methoxy-5-methylsulphonylbenzoic acid (50390-76-6) → 4-(methylsulfonyl)-2-(oxazol-2-yl)phenol

Conditions	Yield
Multi-step reaction with 5 steps 1: thionyl chloride / 3 h / Reflux; Inert atmosphere 2: triethylamine / dichloromethane / 20 °C 3: hydrogenchloride / acetone; water / 5 h / Reflux 4: Burgess Reagent / tetrahydrofuran / 0.17 h / 70 °C / Microwave irradiation 5: boron tribromide / dichloromethane / 0 - 20 °C View Scheme

Upstream product

• 50390-78-8 4-methoxy-3-methylphenyl methyl sulphide 
• 61694-97-1 2-methoxy-5-(methylthio)benzoic acid 
• 51904-91-7 5-chlorosulfonyl-2-anisic acid 
• 79-11-8 chloroacetic acid 
• 698-32-8 4-methoxy-3-methylbenzenethiol 
• 80530-56-9 5-mercapto-2-methoxybenzoic acid 
• 84910-98-5 4-methoxy-3-methylbenzene-1-sulfonyl chloride 
• 63484-12-8 methyl 2-(methyloxy)-5-(methylsulfonyl)benzoate 

Downstream Products

• 94134-08-4 C₁₂H₁₄O₇S 
• 61694-34-6 N-[2-(N'-benzyl-N'-methylamino)ethyl]-6-methoxy-3-methylsulfonylbenzamide 
• 51012-32-9 tiapride 
• 1229627-87-5 3-fluoro-4-[4-(5-methanesulfonyl-2-methoxy-benzoyl)-piperazin-1-yl]-benzonitrile 
• 1297600-41-9 C₂HF₃O₂*C₁₅H₂₄N₂O₄S₃ 
• 294860-49-4 2-(bromomethyl)-1-methoxy-4-(methylsulfonyl)benzene 
• 54110-33-7 2-methoxy-5-methyl sulphonyl-benzoyl chloride 

Relevant articles and documents

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