(R)-N-(2-(1-(3-Ethoxy-4-methoxyphenyl)-2-(methylsulfonyl)ethyl)-1,3-dioxoisoindolin-4-yl)acetamide

Base Information

• Chemical Name: (R)-N-(2-(1-(3-Ethoxy-4-methoxyphenyl)-2-(methylsulfonyl)ethyl)-1,3-dioxoisoindolin-4-yl)acetamide
• CAS No.: 608141-44-2
• Molecular Formula: C₂₂H₂₄N₂O₇S
• Molecular Weight: 460.508
• Mol file: 608141-44-2.mol

Synonyms:R-Apremilast

Chemical Property of (R)-N-(2-(1-(3-Ethoxy-4-methoxyphenyl)-2-(methylsulfonyl)ethyl)-1,3-dioxoisoindolin-4-yl)acetamide

Chemical Property:

• Melting Point: >75°C (dec.)
• Boiling Point: 741.3±60.0 °C(Predicted)
• PKA: 14.01±0.20(Predicted)
• Density: 1.381±0.06 g/cm3(Predicted)
• Storage Temp.: Refrigerator
• Solubility.: Chloroform (Slightly), Methanol (Slightly)

Purity/Quality:

98% min ^*data from raw suppliers

(R)-Apremilast ^*data from reagent suppliers

Safty Information:

• Pictogram(s):  
• Hazard Codes: 

MSDS Files:

SDS file from LookChem

Useful:

• Uses: (R)-Apremilast is an enantiomer of Apremilast (A729700), an oral phosphodiesterase 4 inhibitor is used in the treatment of psoriatic arthritis.

Technology Process of (R)-N-(2-(1-(3-Ethoxy-4-methoxyphenyl)-2-(methylsulfonyl)ethyl)-1,3-dioxoisoindolin-4-yl)acetamide

There total 23 articles about (R)-N-(2-(1-(3-Ethoxy-4-methoxyphenyl)-2-(methylsulfonyl)ethyl)-1,3-dioxoisoindolin-4-yl)acetamide which guide to synthetic route it. The literature collected by LookChem mainly comes from the sharing of users and the free literature resources found by Internet computing technology. We keep the original model of the professional version of literature to make it easier and faster for users to retrieve and use. At the same time, we analyze and calculate the most feasible synthesis route with the highest yield for your reference as below:

synthetic route:

Reference yield: 78.0%

3-acetylaminophthalic anhydride (6296-53-3) + (R)-1-(3-ethoxy-4-methoxyphenyl)-2-(methylsulfonyl)-ethylamine (608142-27-4) → R-Apremilast (608141-44-2)

Guidance literature:

With acetic acid; Microwave irradiation;

DOI:10.1002/cctc.201901473

Reference yield: 65.0%

3-acetamidophthalimide (6118-65-6) + (R)-3-ethoxy-4-methoxy-α-[(methylsulfonyl)methyl]benzyl alcohol (1450657-24-5) → Apremilast (608141-41-9) + R-Apremilast (608141-44-2)

Guidance literature:

With di-isopropyl azodicarboxylate; triphenylphosphine; In tetrahydrofuran; toluene; at -5 - 20 ℃; for 7h; Inert atmosphere;

DOI:10.21577/0103-5053.20210012

Reference yield:

1-(3-ethoxy-4-methoxyphenyl)-2-(methylsulfonyl)ethan-1-one (1450657-28-9) → Apremilast (608141-41-9) + R-Apremilast (608141-44-2)

Guidance literature:

Multi-step reaction with 2 steps

1: D-glucose / water / 48 h / 30 °C / Enzymatic reaction

2: diethylazodicarboxylate; triphenylphosphine / dichloromethane; toluene / 20 °C / Cooling with ice

With D-glucose; triphenylphosphine; diethylazodicarboxylate; In dichloromethane; water; toluene;

upstream raw materials:

3-acetylaminophthalic anhydride

(R)-1-(3-ethoxy-4-methoxyphenyl)-2-(methylsulfonyl)-ethylamine

3-acetamidophthalimide

(R)-3-ethoxy-4-methoxy-α-[(methylsulfonyl)methyl]benzyl alcohol

Refernces

• 1、 -. "Methods for preparation of apremilast". . . Retrieved 2021/05/19.
• 2、 Syu, Jin-Fong,Gopula, Balraj,Jian, Jia-Hong,Li, Wei-Sian,Kuo, Ting-Shen,Wu, Ping-Yu,Henschke, Julian P.,Hsieh, Meng-Chi,Tsai, Ming-Kang,Wu, Hsyueh-Liang. "Asymmetric Synthesis of β-Aryl β-Imido Sulfones Using Rhodium Catalysts with Chiral Diene Ligands: Synthesis of Apremilast". . p. 4614 - 4618. Retrieved 2019/06/27.