Citation: Lv Haijun, Jin Gengen, Liu Lei, Wang Zihui, Lu Shixian, Wang Tingting. Study on the Synthesis of Formoterol Fumarate[J]. Chemistry, ;2019, 82(2): 133-137. shu

Study on the Synthesis of Formoterol Fumarate

Lv Haijun ¹ ,
Jin Gengen ¹ ,
Liu Lei ^1,2,, ,
Wang Zihui ¹ ,
Lu Shixian ¹ ,
Wang Tingting ¹

1.
Hebei Research Center of Pharmaceutical and Chemical Engineering, College of Chemical and Pharmaceutical Engineering, Hebei University of Science and Technology, Shijiazhuang 050018
2.
Hebei Key Laboratory of Molecular Chemistry for Drug, Shijiazhuang 050018

Corresponding author: Liu Lei, liulei@hebust.edu.cn
Received Date: 30 August 2018
Accepted Date: 20 November 2018

Figures(1)

Formoterol fumarate is widely used as a therapeutic agent in the treatment of asthma. In this work, the synthesis process for preparation of formoterol fumarate was optimized and improved. 4-Benzyloxy-3-nitrophenyloxirane (Intermediate 3), one of the important intermediates, was obtained from 4-hydroxy-3-nitroacetophenone by benzylation, bromination, reduction and epoxidation reactions. During the preparing of intermediate 3, a one-pot method was adopted to simplify the processing. Potassium carbonate as an acid-binding agent was added in the reaction to accelerate the reaction rate and increase the yield. Another important intermediate, 1-(4-methoxyphenyl-2-methylethyl)benzylamine (Intermediate 4) was prepared from p-methoxyphenylacetone by a one-step reductive amination reaction. 3 and 4 were coupled to obtain intermediate 5 under microwave condition in a considerably short period. After nitro reduction, formylation, deprotection and salification, formoterol fumarate was obtained. This optimized method is simple and suitable for industrial production of formoterol fumarate with total yield of 7.46%.
- Formoterol fumarate,
- Microwave synthesis,
- Catalytic hydrogenation,
- Improved synthesis,
- Reduction reaction
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