33045-52-2

Basic information

• Product Name: Methyl 2-methoxy-5-sulfamoylbenzoate
• Synonyms: 5-Aminosulfonyl-2-Methoxy-Benzoic Acid Methyl Ester;2-Methoxy-5-Aminosulfonyl Benzoic Acid Methyl Ester Methyl 2-Methoxy-5-Aminosulfonyl Benzoate;Methyl 5-(aminosulphonyl)-2-methoxybenzoate;METHYL 2-METHOXY-5-SULFAMOYLBENZOATE, 98 %;2-Methoxy-5-sulfamoylbenzoic;2-METHOXY-5-SULFAMIDE METHYL BENZOATE;Methyl[5-Amino Sulfonyl-2-Methoxy];5-(Aminosulfonyl)-2-methoxybenzoic Acid Methyl Ester Methyl 2-Methoxy-5-sulfamoylbenzoate 2-Methoxy-5-sulfamoylbenzoic Acid Methyl Ester
• CAS NO: 33045-52-2
• Molecular Formula: C₉H₁₁NO₅S
• Molecular Weight: 245.25
• EINECS: 251-358-1
• Product Categories: FINE Chemical & INTERMEDIATES;Organic Building Blocks;Sulfonamides/Sulfinamides;Sulfur Compounds
• Mol File: 33045-52-2.mol
• Article Data: 8

Chemical Properties

• Melting Point: 175-177 °C(lit.)
• Boiling Point: 439.8 °C at 760 mmHg
• Flash Point: 219.8 °C
• Appearance: /
• Density: 1.36 g/cm³
• Vapor Pressure: 6.2E-08mmHg at 25°C
• Refractive Index: 1.541
• Storage Temp.: 2-8°C
• Solubility: DMSO (Slightly), Methanol (Slightly)
• PKA: 9.94±0.60(Predicted)
• CAS DataBase Reference: Methyl 2-methoxy-5-sulfamoylbenzoate(CAS DataBase Reference)
• NIST Chemistry Reference: Methyl 2-methoxy-5-sulfamoylbenzoate(33045-52-2)
• EPA Substance Registry System: Methyl 2-methoxy-5-sulfamoylbenzoate(33045-52-2)

Safety Data

• Hazard Codes: Xi
• WGK Germany: 3
• Hazardous Substances Data: 33045-52-2(Hazardous Substances Data)

Usage

Uses

Methyl 2-methoxy-5-sulfamoylbenzoate is a reactant used in the preparation of many pharmaceutical compounds used as anticoagulants, HCV NS5B polymerase inhibitors, therapeutic drugs for treatment of neurodegenerative diseases and oral hypog lycemic agents.

General Description

Methyl 2-methoxy-5-sulfamoylbenzoate is also referred to as 2-methoxy-5-sulfamoyl methyl benzoate or methyl 5-(aminosulphonyl)-2-methoxybenzoate.

InChI:InChI=1/C9H11NO5S/c1-14-8-4-3-6(16(10,12)13)5-7(8)9(11)15-2/h3-5H,1-2H3,(H2,10,12,13)

Synthetic route

methyl 5-chloro-2-methoxybenzoate (33924-48-0) → methyl 2-methoxy-5-sulfamoyl-benzoate (33045-52-2)

Conditions	Yield
With sodium sulfamate; copper(I) bromide In tetrahydrofuran at 50℃; for 10h; Temperature; Reflux;	96.55%
With sodium aminosulfinate; copper(I) bromide In tetrahydrofuran at 40℃; for 18h; Concentration; Temperature;	96.55%
With sodium aminosulfinate; copper(l) chloride In tetrahydrofuran at 40℃; for 8h; Temperature;	96.55%

methanol (67-56-1) + 3-cyano-4-methoxybenzenesulfonamide (22117-84-6) → methyl 2-methoxy-5-sulfamoyl-benzoate (33045-52-2)

Conditions	Yield
With hydrogenchloride at 40℃; for 6h; Time;	88.6%

methanol (67-56-1) + 2-methoxy-5-sulfamoylbenzoic acid (22117-85-7) → methyl 2-methoxy-5-sulfamoyl-benzoate (33045-52-2)

Conditions	Yield
With hydrogenchloride

methyl 2-methoxy-5-sulfamoyl-benzoate (33045-52-2) → 2-methoxy-5-sulfamoylbenzoic acid (22117-85-7)

Conditions	Yield
With sodium hydroxide In methanol	98.3%
Stage #1: methyl 2-methoxy-5-sulfamoyl-benzoate With sodium hydroxide; water In methanol at 20℃; for 1h; Stage #2: With hydrogenchloride In methanol; water	98.3%
Stage #1: methyl 2-methoxy-5-sulfamoyl-benzoate With sodium hydroxide; water In methanol at 20℃; for 1h; Stage #2: With hydrogenchloride In methanol; water	98.3%

ethanol (64-17-5) + methyl 2-methoxy-5-sulfamoyl-benzoate (33045-52-2) → 2-methoxy-5-sulfamoylbenzoic acid ethyl ester (33045-53-3)

Conditions	Yield
With sulfuric acid for 12h; Heating;	98%

methyl 2-methoxy-5-sulfamoyl-benzoate (33045-52-2) + (S)-2-(Aminomethyl)-1-ethylpyrrolidine (22795-99-9) → (S)-(-)-sulpiride (15676-16-1, 23672-06-2, 23672-07-3, 23756-79-8)

Conditions	Yield
at 90 - 100℃; for 5h; Inert atmosphere;	93.8%
With hydrogenchloride In water; butan-1-ol	75%

1-ethyl-2-pyrrolidinemethanamine (26116-12-1) + methyl 2-methoxy-5-sulfamoyl-benzoate (33045-52-2) → N-[(1-ethyl-2-pyrrolidinyl)methyl]-2-methoxy-5-sulfamoylbenzamide (15676-16-1)

Conditions	Yield
In glycerol at 90 - 95℃; for 10h; Inert atmosphere;	88.4%
In ethylene glycol at 90 - 100℃; Solvent; Inert atmosphere;	85.1%
at 100℃; for 3h;	75%

methyl 2-methoxy-5-sulfamoyl-benzoate (33045-52-2) + acetic anhydride (108-24-7) → methyl 5-(N-acetylsulfamoyl)-2-methoxybenzoate

Conditions	Yield
With zinc(II) chloride at 20℃;	77%

aminolupinane (2346-98-7, 10248-19-8, 15527-89-6, 22342-32-1, 46000-58-2, 75532-84-2, 145842-67-7) + methyl 2-methoxy-5-sulfamoyl-benzoate (33045-52-2) → 2-Methoxy-N-[(1S,9aR)-1-(octahydro-quinolizin-1-yl)methyl]-5-sulfamoyl-benzamide

Conditions	Yield
In methanol at 110℃; for 20h;	74.4%

methyl 2-methoxy-5-sulfamoyl-benzoate (33045-52-2) + homo-Lupinylamine → 5-Aminosulfonyl-2-methoxy-N-[2-(1α-quinolizidinyl)ethyl]-benzamide

Conditions	Yield
In methanol at 110℃; for 24h;	64%

3-(3,4-dichlorobenzylthio)thiophene-2-carboxylic acid (251096-84-1) + methyl 2-methoxy-5-sulfamoyl-benzoate (33045-52-2) → methyl 5-(N-(3-(3,4-dichlorobenzylthio)thiophene-2-carbonyl)sulfamoyl)-2-methoxybenzoate (1336982-58-1)

Conditions	Yield
With dmap; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride In N,N-dimethyl-formamide at 25℃; for 6h; Inert atmosphere;	23%

methyl 2-methoxy-5-sulfamoyl-benzoate (33045-52-2) + (+/-)-epilupinamine (2346-98-7, 10248-19-8, 15527-89-6, 22342-32-1, 46000-58-2, 75532-84-2, 145842-67-7) → 5-Aminosulfonyl-N-(1-epi-lupinyl)-2-methoxybenzamide

Conditions	Yield
In methanol at 110℃; for 24h; Yield given;

methyl 2-methoxy-5-sulfamoyl-benzoate (33045-52-2) → N-benzyl-5-(aminosulfonyl)-2-methoxybenzamide (113681-63-3)

Conditions	Yield
Multi-step reaction with 2 steps 1: 98 percent / H2SO4 / 12 h / Heating 2: 5 percent / sodium methoxide / 5 h / 100 °C View Scheme

methyl 2-methoxy-5-sulfamoyl-benzoate (33045-52-2) → N-(1-methyl-4-piperidinyl)-5-(aminosulfonyl)-2-methoxybenzamide (113681-64-4)

Conditions	Yield
Multi-step reaction with 2 steps 1: 98 percent / H2SO4 / 12 h / Heating 2: 54 percent / NaH / 1.) 100 deg C, 5 h; 2.) 120-130 deg C, 6 h View Scheme

1-cyclopentyl 2-aminomethyl pyrrolidine + methyl 2-methoxy-5-sulfamoyl-benzoate (33045-52-2) → benzamide (55-21-0)

Conditions	Yield
In water; ethylene glycol; acetic acid

methyl 2-methoxy-5-sulfamoyl-benzoate (33045-52-2) → 3-(Hydroxymethyl)-4-methoxybenzenesulfonamide (900165-91-5)

Conditions	Yield
With lithium borohydride In tetrahydrofuran; methanol at 20℃; for 8h;

methyl 2-methoxy-5-sulfamoyl-benzoate (33045-52-2) → dimethyl 2-(2-(N-acetylsulfamoyl)-5-methoxy-4-(methoxycarbonyl)phenyl)malonate

Conditions	Yield
Multi-step reaction with 2 steps 1: zinc(II) chloride / 20 °C 2: silver(I) acetate; dichloro(pentamethylcyclopentadienyl)rhodium (III) dimer / 1,2-dichloro-ethane / 5 h / 60 °C / Sealed tube View Scheme

Upstream product

• 67-56-1 methanol 
• 22117-85-7 2-methoxy-5-sulfamoylbenzoic acid 
• 22117-84-6 3-cyano-4-methoxybenzenesulfonamide 
• 33924-48-0 methyl 5-chloro-2-methoxybenzoate 

Downstream Products

• 177027-05-3 2-Methoxy-N-[(1S,9aR)-1-(octahydro-quinolizin-1-yl)methyl]-5-sulfamoyl-benzamide 
• 177027-05-3 5-Aminosulfonyl-N-(1-epi-lupinyl)-2-methoxybenzamide 
• 55-21-0 benzamide 
• 900165-91-5 3-(Hydroxymethyl)-4-methoxybenzenesulfonamide 
• 1336982-58-1 methyl 5-(N-(3-(3,4-dichlorobenzylthio)thiophene-2-carbonyl)sulfamoyl)-2-methoxybenzoate 
• 15676-16-1 (S)-(-)-sulpiride 
• 22117-85-7 2-methoxy-5-sulfamoylbenzoic acid 
• 113681-64-4 N-(1-methyl-4-piperidinyl)-5-(aminosulfonyl)-2-methoxybenzamide 
• 113681-63-3 N-benzyl-5-(aminosulfonyl)-2-methoxybenzamide 
• 15676-16-1 N-[(1-ethyl-2-pyrrolidinyl)methyl]-2-methoxy-5-sulfamoylbenzamide 
• 33045-53-3 2-methoxy-5-sulfamoylbenzoic acid ethyl ester 

Relevant articles and documents

Preparation method of 2-methoxy-5-sulfamoylbenzoic acid

The invention provides a preparation method of 2-methoxy-5-sulfamoylbenzoic acid, comprising the following steps: carrying out bromination reaction on 4-methoxybenzenesulfonamide and bromine under theaction of a reducing agent to obtain 3-bromo-4-methoxybenzenesulfonamide; carrying out substitution reaction on 3-bromo-4-methoxybenzenesulfonamide and cuprous cyanide under the action of a catalystto generate 3-cyano-4-methoxybenzenesulfonamide; carrying out alcoholysis on the 3-cyano-4-methoxybenzenesulfonamide and methanol under the catalysis of an acid to obtain 2-methoxy-5-sulfonamide methyl benzoate; hydrolyzing 2-methoxy-5-sulfonamide methyl benzoate under an alkaline condition, and then acidifying to obtain the 2-methoxy-5-sulfamoylbenzoic acid. The preparation method of the 2-methoxy-5-sulfamoylbenzoic acid is mild in reaction condition, simple in process and equipment, convenient to operate and environmentally friendly.

Method for conveniently synthesizing 2-methoxy-5-sulfamoyl methyl benzoate

The invention provides a method for conveniently synthesizing 2-methoxy-5-sulfamoyl methyl benzoate. The method comprises the following steps: adding 2-methoxyl-5-chloro methyl benzoate and sodium aminosulfinic acid in a molar ratio of 1: (1 to 1.1) as well as a solvent and a catalyst into a reaction device, controlling the temperature at 40 to 65 DEG C, and reacting for 12 to 18 hours; after the reaction is ended, adding activated carbon to perform decoloring, and filtering to remove the activated carbon, catalyst and side product sodium chloride; decompressing and concentrating filtrate to obtain the 2-methoxy-5-sulfamoyl methyl benzoate. The method for conveniently synthesizing the 2-methoxy-5-sulfamoyl methyl benzoate has the advantages that the technical flow is short, the yield is high, the quality is good, the three wastes (waste gas, waste water and industrial residue) polluting the environment are avoided, and the method is environment-friendly and suitable for the industrialized mass production.

Method for synthesizing 2-methoxy-5-sulfamoylmethyl benzoate

The invention provides a method for synthesizing 2-methoxy-5-sulfamoyl methyl benzoate. The method comprises the following steps: adding 2-methoxy-5-chlorobenzene methyl formate and sodium aminosulfinate at the mol ratio of 1:1.05-1.2 and a solvent and a catalyst into a reactor, controlling temperature at 40-65 DEG C and reacting for 8-16 h; carrying out decoloration by adding active carbon after the reaction, filtering to remove active carbon, the catalyst and a by-product sodium chloride; and carrying out vacuum concentration on a filtrate so as to obtain 2-methoxy-5-sulfamoyl methyl benzoate. The method for synthesizing 2-methoxy-5-sulfamoyl methyl benzoate has advantages of short original process flow, high yield and good quality. In addition, ''three wastes (waste gas, waste water and industrial residue)'' which pollute the environment are not generated. The method is very environmentally friendly and is suitable for large-scale industrial production.