253168-94-4Relevant articles and documents
Synthetic method of apremilast intermediate
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, (2021/04/26)
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.
CRYSTAL FORMS OF THIOPHENE DERIVATIVES
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Paragraph 0268; 0269, (2021/05/14)
Disclosed is crystal form I of compound (S)—N-[5-[1-(3-ethoxy-4-methoxyphenyl)-2-(methylsulfonyl)ethyl]-4,6-dioxo-5,6-dihydro-4H-thieno[3,4-c]pyrrole-1-yl]acetamide.
RACEMIC BETA-AMINOSULFONE COMPOUNDS
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Paragraph 0057-0058, (2020/03/28)
It is described an industrially viable and advantageous process for the preparation of racemic beta-aminosulfone (1), an useful intermediate for the preparation of N-(2-((1S)-1-(3-ethoxy-4-methoxyphenyl)-2-(methylsulfonyl)ethyl)-2,3-dihydro-1,3-dioxo-1H-isoindol-4-yl)acetamide, also known as Apremilast, the latter being suitable for use in methods of treating, preventing and/or managing psoriasis or psoriatic arthritis.
Synthesis of Substituted β-Functionalised Styrenes by Microwave-Assisted Olefin Cross-Metathesis and Scalable Synthesis of Apremilast
Jana, Anupam,Zieliński, Grzegorz Krzysztof,Czarnocka-?niada?a, Sylwia,Grudzień, Krzysztof,Podwysocka, Dominika,Szulc, Marcin,Kajetanowicz, Anna,Grela, Karol
, p. 5808 - 5813 (2019/11/03)
Preparation of diversely substituted β-functionalised styrenes by microwave-assisted olefin cross-metathesis (CM) is described. This method can be also employed in the synthesis of β-deuterated α,β-unsaturated sulfones from inexpensive allylbenzenes, though unprecedented one-pot isomerisation/deuteration/cross-metathesis sequence. One of such obtained CM products has been utilised in a new scalable synthesis of Apremilast (6), a potent and orally active phosphodiesterase 4 and tumour necrosis factor-α inhibitor. The same strategy was used in synthesis of an optical antipode of 6, ent-Apremilast.
Method for preparing intermediate of Apremilast
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Paragraph 0032-0035, (2019/03/26)
The invention provides a method for preparing an intermediate 1-(3-ethoxy-4-methoxyphenyl)-2-methylsulfonylethylamine (I), shown in a following figure, of Apremilast. The method comprises the following steps: (1) adding dimethyl sulfone in a suitable solvent, and performing a reaction with an organolithium compound at -40-10 DEG C for 0.5-2 hours so as to obtain a reaction liquid R1; (2) adding 3-ethoxy-4-methoxybenzaldehyde in a suitable solvent, and performing a reaction with a weak-nucleophilicity strong base at -40-10 DEG C for 0.5-2 hours so as to obtain a reaction liquid R2; (3) adding the R2 into R1 dropwise, and performing a reaction at -60-0 DEG C for 0.5-2 hours so as to obtain a reaction liquid R3; (4) adding boron trifluoride diethyl etherate to the R3, and performing a reaction at -80-0 DEG C; (5) quenching the reaction, performing filtration, performing pulping and washing on the obtained filter cake by using dichloromethane, performing extraction on the aqueous layer with the dichloromethane, combining the organic layer, and performing concentration; (6) adding dichloromethane to the residues obtained after concentration, performing washing with acid water, and performing liquid separation; and (7) adjusting the pH value of the water layer to 10-14, performing extraction with dichloromethane, and concentrating the organic layer so as to obtain the 1-(3-ethoxy-4-methoxyphenyl)-2-methylsulfonylethylamine crude product. The method is based on a synthetic method firstly reported by an original research company, the feeding mode and feeding ratio are changed, control on reaction conditions is achieved, and the method has high operability, and is conducive to large-scale industrial production.
Method for synthesizing 1-(3-ethyoxyl-4-methoxy)phenyl-2-methyl-sulfonyl ethylamine
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, (2018/11/22)
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.
Copper-Catalyzed Synthesis of β-Azido Sulfonates or Fluorinated Alkanes: Divergent Reactivity of Sodium Sulfinates
Xiong, Yang,Sun, Youwen,Zhang, Guozhu
supporting information, p. 6250 - 6254 (2018/10/05)
A new and general method for the synthesis of β-azidosulfonates has been achieved through Cu(I)-mediated radical oxidative sulfonylation-azidation of alkenes with sodium sulfinates. Under identical conditions, azido fluoroalkyated products could be readily obtained instead using CF3SO2Na or CHF2SO2Na as reagents. The starting materials of sulfinate compounds, alkenes, and azidotrimethylsilane are stable and cheap. This method can be easily adapted for large-scale preparation.
NOVEL PROCESS FOR THE PREPARATION OF 1-(3-ETHOXY-4-METHOXY-PHENYL)-2-METHYLSULFONYL-ETHANAMINE
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, (2018/04/17)
The present invention relates to a process for the preparation of 1-(3-ethoxy-4-methoxy-phenyl)-2-methylsulfonyl-ethanamine, an intermediate for the preparation of apremilast via a compound of Formula (V) wherein R is (C1-C4)alkyl, (C1-C4)haloalkyl, -O(C1-C4)alkyl, or –O-benzyl, and L is a leaving group.
NOVEL PROCESS FOR PREPARATION OF APREMILAST
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Page/Page column 14; 15, (2018/02/03)
The present invention related to a novel compound of Formula II, its enantiomers or acid addition salts thereof and process for its preparation. The compound of Formula II can be used for preparation of N-[2-[(1S)-1-(3-ethoxy-4-methoxyphenyl)-2- (methylsulfonyl)ethyl]-2,3-dihydro-1,3-dioxo-1H-isoindol-4-yl]acetamide also known as apremilast.
Preparation method of 2-(methyl sulphonyl)-1-aromatic ethylamine
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Paragraph 0011, (2017/08/28)
The invention provides a novel preparation method of 2-(methyl sulphonyl)-1-aromatic ethylamine as shown in a formula (II) defined in the description. The method comprises the step that R substituted benzaldehyde, 2-(methyl sulphonyl)acetic acid and ammonium acetate which are as shown in a formula (I) defined in the description serve as raw materials to synthesize 2-(methyl sulphonyl)-1-aromatic ethylamine as shown in the formula (II) defined in the description. By means of the method, the defects that similar products are high in production cost, strict in condition, low in yield and the like are overcome, and great application value and economic benefit are achieved.
