Preparation method of Apremilast
A technology of apremilast and preparation steps, which is applied in the field of preparation of apremilast, can solve the problems of harsh reaction conditions, long reaction steps, unfavorable industrialization, etc., and achieve the effects of easy availability of raw materials, promotion of development, and simple process
Active Publication Date: 2014-06-18
徐州鑫辉生物能源科技有限公司
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The invention discloses a preparation method of Apremilast (I). The preparation method comprises the following steps: carrying out condensation on (R)-1-(Alpha-amino-benzyl)-2-isonaphthol (II) and 3-ethyoxyl-4-methoxybenaldehyde (III) to generate (1R, 3S)-1-phenyl-3-(3-ethyoxyl-4-methoxyphenyl)-2,3-dihydro-1H-naphthyl[1, 2-e][1, 3] oxazine (IV), carrying out cycloaddition reaction on the intermediate (IV) and a dimethyl sulfone organolithium salt to generate N-[(2S)-(1-(3-ethyoxyl-4-methoxyphenyl)-2-methylsulfonyl ethyl)]-(1R)-(Alpha-amino-benzyl)-2-isonaphthol (V), carrying out a hydrogenation reduction reaction on the intermediate (V) to prepare (S)-2-[1-(3- ethyoxyl-4-methoxyphenyl)]-1-methylsulfonyl-2-ethylamine (intermediate B), and carrying out condensation on the intermediate B and 3-acetamido phthalic anhydride (intermediate A) to prepare the Apremilast (I). The preparation method disclosed by the invention uses easily available raw materials and concise process, is economical, environment-friendly and suitable for industrial production.
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SulfoneEthylamines +5
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