Background and overview[1]
1-(3-ethoxy-4-methoxyphenyl)-2-(methanesulfonyl)ethanone can be used to prepare the Apremilast intermediate 1-(3-ethoxy-4- Methoxy)phenyl-2-methanesulfonylethylamine. As an oral small molecule PDE-4 inhibitor, Apremilast is cheaper and more convenient than biologics for injection; it has good safety profile: it has fewer side effects than other PDE-4 inhibitors, and it expands the applicable population. Therefore, Apremilast has a large market space as a treatment for psoriatic arthritis.
Preparation[1]
Preparation of 1-(3-ethoxy-4-methoxy)phenyl-2-methanesulfonylethanone
Into a dry 100mL three-necked flask, add 2.1g methyl 3-ethoxy-4-methoxybenzoate, 1.88g dimethyl sulfone, and 2.24g potassium tert-butoxide in sequence, and add molecular sieves under nitrogen protection. Take 15 mL of dried dimethyl sulfoxide, heat it to 50°C, and react under magnetic stirring for 1.5 hours. After the reaction is completed, transfer the product to a beaker and add 80 mL of ice water and 4.2 mL of concentrated hydrochloric acid. After filtration, recover the filtrate and extract with ether to obtain the solid product 1-(3-ethoxy -4-Methoxy)phenyl-2-methanesulfonylethanone 1.11g, yield 40.7%.
Apply[1]
It can be used to prepare 1-(3-ethoxy-4-methoxy)phenyl-2-methanesulfonylethylamine.
Add 1.36g 1-(3-ethoxy-4-methoxy)phenyl-2-methanesulfonylethanone, 3.15g ammonium formate, 40mL methanol, and 4mL water in sequence into a 100mL single-neck flask, and reflux Reaction 20h. Wash the filter residue after the reaction with 10 mL of methanol. After distilling off the solvent under reduced pressure, add 25 mL of water and 25 mL of methylene chloride to the filtrate to extract, and then extract with 30 mL of methylene chloride three times. Combine the organic phases and wash with 20 mL of saturated brine. , dried over anhydrous sodium sulfate and then filtered. The filtrate was distilled off under reduced pressure to remove the solvent. The residue was washed with 10 mL of ethyl acetate. After cooling and crystallizing, it was stirred at room temperature for 0.5h. After filtration, a white solid 1-(3-ethoxy- 0.58g of 4-methoxy)phenyl-2-methanesulfonylethylamine, yield 42.4%.
Main reference materials
[1] CN201810780737.8 A method for synthesizing 1-(3-ethoxy-4-methoxy)phenyl-2-methanesulfonylethylamine
