1450657-28-9

Basic information

• Product Name: 1-(3-Ethoxy-4-Methoxyphenyl)-2-(Methylsulfonyl) ethanone
• Synonyms: 1-(3-Ethoxy-4-Methoxyphenyl)-2-(Methylsulfonyl) ethanone;1-(3-Ethoxy-4-methoxy-phenyl)-2-methanesulfonyl-ethanone
• CAS NO: 1450657-28-9
• Molecular Formula: C₁₂H₁₆O₅S
• Molecular Weight: 272.31744
• EINECS: -0
• Product Categories: ApreMilast;apremilast intermediates
• Mol File: 1450657-28-9.mol

Chemical Properties

• Appearance: /
• Storage Temp.: -20°C Freezer
• Solubility: Chloroform (Slightly), Methanol (Slightly)
• CAS DataBase Reference: 1-(3-Ethoxy-4-Methoxyphenyl)-2-(Methylsulfonyl) ethanone(CAS DataBase Reference)
• NIST Chemistry Reference: 1-(3-Ethoxy-4-Methoxyphenyl)-2-(Methylsulfonyl) ethanone(1450657-28-9)
• EPA Substance Registry System: 1-(3-Ethoxy-4-Methoxyphenyl)-2-(Methylsulfonyl) ethanone(1450657-28-9)

Safety Data

• Hazardous Substances Data: 1450657-28-9(Hazardous Substances Data)

Usage

Uses

Used in Pharmaceutical Industry:
EMSO is used as a key building block for the synthesis of various pharmaceutical products due to its unique chemical structure that can be further modified to create a range of medicinal compounds.
Used in Agrochemical Industry:
In the agrochemical sector, EMSO serves as a fundamental component in the development of new agrochemicals, contributing to the creation of more effective and targeted crop protection agents.
Used in Organic Compound Production:
EMSO is utilized as an intermediate in the production of organic compounds, playing a crucial role in the synthesis of a variety of chemical entities that find applications in different industries.
Used in Chemical Reactions as a Reagent:
As a reagent, EMSO is employed in various chemical reactions to facilitate specific transformations, making it an indispensable tool in the synthesis of complex organic molecules.

Upstream product

• 2386-57-4 methanesulfonic acid sodium salt 
• 6100-74-9 3-hydroxy-4-methoxyacetophenone 
• 31526-71-3 3-ethoxy-4-methoxy-acetophenone 
• 67-71-0 dimethylsulfone 
• 97966-31-9 3-ethoxy-4-methoxybenzoic acid methyl ester 
• 20277-69-4 sodium methansulfinate 
• 1131-52-8 3-ethoxy-4-methoxybenzaldehyde 
• 6702-50-7 3-hydroxy-4-methoxybenzoate 
• 645-08-9 Isovanillic acid 
• 74-96-4 ethyl bromide 
• 613-70-7 2-methoxyphenyl acetate 
• 881919-82-0 3-ethoxy-4-methoxyphenylacetylene 
• 253168-94-4 2-(3-ethoxy-4-methoxyphenyl)-1-(methylsulfonyl)eth-2-ylamine 
• 124-63-0 methanesulfonyl chloride 

Downstream Products

• 1450657-24-5 (R)-3-ethoxy-4-methoxy-α-[(methylsulfonyl)methyl]benzyl alcohol 
• 608141-43-1 (S)-1-(3-ethoxy-4-methoxyphenyl)-2-(methylsulfonyl)ethanamine-(S)-2-acetamido-4-methylpentanoate 
• 1450657-43-8 (S)-4-(1-azido-2-(methylsulfonyl)ethyl)-2-ethoxy-1-methoxybenzene 
• 608141-41-9 Apremilast 
• 253168-94-4 2-(3-ethoxy-4-methoxyphenyl)-1-(methylsulfonyl)eth-2-ylamine 
• 635705-72-5 4-amino-2-[(1S)-1-(3-ethoxy 4-methoxyphenyl)-2-methanesulfonylethyl]-2,3-dihydro-1H-isoindole-1,3-dione 
• 608141-44-2 R-Apremilast 
• 608141-42-0 (S)-2-[1 (3-ethoxy-4-methoxyphenyl)]-1-methanesulfonyl-2-ethylamine 
• 1450759-47-3 (1S,1'S)-[1-(3-ethoxy-4-methoxyphenyl)-2-methanesulfonyl]ethyl-N-(1'-phenylethyl)amine hydrochloride 

Relevant articles and documents

Directed evolution of an amine transaminase for the synthesis of an Apremilast intermediate via kinetic resolution

Apremilast is an important active pharmaceutical ingredient that relies on a resolution to produce the key chiral amine intermediate. To provide a new catalytic and enzymatic process for Apremilast, we performed the directed evolution of the amine transaminase from Vibrio fluvialis. Six rounds of evolution resulted in the VF-8M-E variant with > 400-fold increase specific activity over the wildtype enzyme. A homology model of VF-8M-E was built and a molecular docking study was performed to explain the increase in activity. The purified VF-8M-E was successfully applied to produce the key chiral amine intermediate in enantiopure form and 49% conversion via a kinetic resolution, representing a new enzymatic access towards Apremilast.

Synthetic method of apremilast intermediate

The invention discloses a synthetic method of an apremilast intermediate. The method comprises the following steps of by taking 2-methoxyphenyl acetate and 2-(methylsulfonyl) acetyl chloride as starting materials, carrying out acylation reaction and hydrolysis under the catalysis of aluminum trichloride to obtain 1-(3-hydroxy-4-methoxyphenyl)-2-(methylsulfonyl) ethyl ketone, carrying out alkylation reaction with bromoethane, and then forming imine with ammonium acetate, and reducing to form the 1-(3-ethoxy-4-methoxy phenyl)-2-(methylsulfonyl) ethylamine. The method is simple to operate, avoids the use of n-butyllithium, palladium on carbon and mesylate, avoids the problems of high risk, high cost and the like, and is suitable for industrial production.

Chemoenzymatic Oxosulfonylation-Bioreduction Sequence for the Stereoselective Synthesis of β-Hydroxy Sulfones

A series of optically active β-hydroxy sulfones has been obtained through an oxosulfonylation-stereoselective reduction sequence in aqueous medium. Firstly, β-keto sulfones were synthesized from arylacetylenes and sodium sulfinates to subsequently develop the carbonyl reduction in a highly selective fashion using alcohol dehydrogenases as biocatalysts. Optimization of the chemical oxosulfonylation reaction was investigated, finding inexpensive iron(III) chloride hexahydrate (FeCl3 ? 6H2O) as the catalyst of choice. The selection of isopropanol in the alcohol-water media resulted in high compatibility with the enzymatic process for enzyme cofactor recycling purposes, providing a straightforward access to both (R)- and (S)-β-hydroxy sulfones. The practical usefulness of this transformation was illustrated by describing the synthesis of a chiral intermediate of Apremilast. Interestingly, the development of a chemoenzymatic cascade approach avoided the isolation of β-keto sulfone intermediates, which allowed the preparation of chiral β-hydroxy sulfones in high conversion values (83–94 %) and excellent optical purities (94 to >99 % ee).

Method for synthesizing 1-(3-ethyoxyl-4-methoxy)phenyl-2-methyl-sulfonyl ethylamine

The invention discloses a method for synthesizing 1-(3-ethyoxyl-4-methoxy)phenyl-2-methyl-sulfonyl ethylamine and belongs to the technical field of organic synthesis processes. The method comprises the following steps: taking 3-hydroxy-4-methoxybenzoic acid as a raw material, carrying out an esterification reaction to obtain 3-hydroxy-4-methoxybenzoate, reacting with bromoethane to obtain 3-ethyoxyl-4-methoxybenzoate, then reacting with dimethyl sulfone to obtain 1-(3-ethyoxyl-4-methoxy)phenyl-2-methyl sulfonyl ethyl ketone, and finally carrying out a reductive amination reaction with ammoniumformate, thereby obtaining the 1-(3-ethyoxyl-4-methoxy)phenyl-2-methyl-sulfonyl ethylamine.

For treating psoriasis sexual arthritis disease apps is special synthetic method (by machine translation)

The invention discloses a method for treating psoriasis sexual arthritis disease apps is special synthetic method, the method to 3 - ethoxy - 4 - methoxybenzaldehyde as the starting material, by with the dimethyl sulfone, n-butyl reaction, to obtain 3 - ethoxy - 4 - methoxy - α - [(methylsulfonyl) methyl] - benzene methanol, through the oxidation reaction to obtain 1 - (3 - ethoxy - 4 - methoxyphenyl) - 2 - methyl-sulfonyl - ethanone, through the reduction reaction to obtain the R - 3 - ethoxy - 4 - methoxy - α - [(methylsulfonyl) methyl] - benzene methanol, finally with 3 - acetamide group ortho-phthalic acid imide by Mitsunobu reaction, to obtain the target product apps is special. The invention has mild reaction condition, the process is simple, the yield is good, easy industrialization and the like. (by machine translation)

A SYNTHETIC PATHWAY TOWARDS APREMILAST

The present invention relates to an asymmetric process for providing N-{2-[(1S)-1-(3-ethoxy-4-methoxyphenyl)-2-(methylsulfonyl)ethyl]-1,3-dioxo-2,3-dihydro-1H-isoindol-4-yl}acetamide (apremilast) or a pharmaceutically acceptable salt or solvate thereof.

A synthetic apps is special method for the preparation of intermediates

The invention relates to a preparation method for synthesizing an apremilast intermediate. The preparation method comprises the following steps of: carrying out condensation reaction on 3-ethoxyl-4-methoxyl-benzoate and dimethyl sulfone under an alkaline condition to generate 2-(3-ethoxy-4-methoxyphenyl)-1-methylsulfonyl acetone; reacting the compound II and chiral amine in the presence of an acidic catalyst to obtain 1-N-substituted amino-1-(3-ethoxyl-4-methoxyl) phenyl-2-methylsulfonyl ethylene (III), and directly hydrogenating the obtained compound III in the presence of a hydrogenation catalyst without separating the compound III to obtain a product (S)-1-(3-ethoxyl-4-methoxyl) phenyl-2-methanesulfonyl ethylamine (I), namely the apremilast intermediate, wherein the apremilast intermediate can be further prepared into N-acetyl L-leucinate. The invention also provides a preparation method of apremilast. The preparation method disclosed by the invention has the advantages of simple process flow, safety, environmental friendliness and low cost and is favorable to clean industrialized production.

Preparation method of Apremilast and intermediate

The invention provides a preparation method of Apremilast and its intermediate. The invention provides an Apremilast intermediate as shown in the formula III. According to the preparation method, the compound as shown in the formula III reacts with methanesulfinate to obtain a compound as shown in the formula IV; the compound as shown in the formula IV undergoes reductive amination to obtain a compound as shown in the formula V; the compound as shown in the formula V and asymmetry acid undergo salifying to obtain a compound as shown in the formula VI; and the compound as shown in the formula VI reacts with 3-acetamido-phthalic anhydride to obtain Apremilast. By the method for synthesizing Apremilast, usage of an n-butyllithium hexane solution can be avoided. Production cost is reduced, and operation process is convenient. In addition, safety in the industrial production is raised to a great extent, and the preparation method is more suitable for industrial continuous production. According to the preparation method of 3-acetamido-phthalic anhydride, yield is raised to 81%. As the yield is high, the method provided by the invention is extremely suitable for industrial production of Apremilast.

A process for synthesizing intermediates apps special chiral amine

The invention relates to a novel process for synthesizing an apremilast chiral amine intermediate (S)-2-[1-(3-ethyoxyl-4-methoxy phenyl)]-1-methylsulfonyl-2-ethylamine (VI). The novel process is characterized in that 1-(3-ethyoxyl-4-methoxy phenyl) ethanone (I) serving as raw material is subjected to reduction and deprotection by using methylsulfonyl ethanone (III) and enamine (IV) to obtain the chiral amine intermediate (VI) with high chiral purity. By adopting the method, the process is efficiently simplified and the technological level and the operability are increased; in addition, the process is mild in reaction condition and good in safety; the yield and purity of the products are high; therefore, the process can be put into large-scale industrial production favorably.