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
1. [1]
2. [2]
  R A Bartow, R N Brogden. Drugs, 1998, 55(2): 303~322.
3. [3]
  J Trofast, K Osterberg, B L Källsträm et al. Chirality, 1991, 3(6): 443~450.
4. [4]
5. [5]
  F Campos, M P Bosch, A Guerrero. Tetrahed. Asymmetry, 2000, 11(13): 2705~2717.
6. [6]
7. [7]
8. [8]
9. [9]
  P D de Koning, I R Gladwell, I B Moses et al. Org. Proc. Res. Dev., 2011, 15(6): 1247~1255.
10. [10]
  H Ling, S Wenjun, Z Qi et al. Bioorg. Med. Chem. Lett., 2014, 24(1): 249~253.
11. [11]
  J W Trofast, E Jakupovic, K L Mansson. USP: 5434304, 1995.
12. [12]
  I Navarro Muñoz, J Huguet Clotet. EPP: 2348013, 2011.
13. [13]
  Y Gao, R Hett, K Q Fang et al. USP: 6268533, 2001.
14. [14]
  S B Bhirud, S M Kadam, S B Gavhane et al. WOP: 2014184756, 2014.
15. [15]
  C Li, Y Li, Y Zhang et al. Anal. Methods, 2018, 10: 548~553.
16. [16]
1. [1]
  Haifeng Ma , Xiaocong Tian , Fengbin Wang , Zhonghua Xi , QingWang . Design of College Chemistry Experiment Based on Product Quality Control: Taking “Optimization of Ferrous Fumarate Synthesis Process” as an Example. University Chemistry, 2025, 40(7): 321-327. doi: 10.12461/PKU.DXHX202409056
2. [2]
  Lewang Yuan , Yaoyao Peng , Zong-Jie Guan , Yu Fang . Insights into the development of 2D covalent organic frameworks as photocatalysts in organic synthesis. Acta Physico-Chimica Sinica, 2025, 41(8): 100086-0. doi: 10.1016/j.actphy.2025.100086
3. [3]
  Yuena Yu , Fang Fang . Microwave-Assisted Synthesis of Safinamide Methanesulfonate. University Chemistry, 2024, 39(11): 210-216. doi: 10.3866/PKU.DXHX202401076
4. [4]
  Guodong Xu , Chengcai Sheng , Xiaomeng Zhao , Tuojiang Zhang , Zongtang Liu , Jun Dong . Reform of Comprehensive Organic Chemistry Experiments in the Context of Emerging Engineering Education: A Case Study on the Improved Preparation of Benzocaine. University Chemistry, 2024, 39(11): 286-295. doi: 10.12461/PKU.DXHX202403094
5. [5]
  Yan Kong , Wei Wei , Lekai Xu , Chen Chen . Electrochemical Synthesis of Organonitrogen Compounds from N-integrated CO₂ Reduction Reaction. Acta Physico-Chimica Sinica, 2024, 40(8): 2307049-0. doi: 10.3866/PKU.WHXB202307049
6. [6]
  Hailian Tang , Siyuan Chen , Qiaoyun Liu , Guoyi Bai , Botao Qiao , Liu Fei . Stabilized Rh/hydroxyapatite Catalyst for Furfuryl Alcohol Hydrogenation: Application of Oxidative Strong Metal-Support Interactions in Reducing Conditions. Acta Physico-Chimica Sinica, 2025, 41(4): 2408004-0. doi: 10.3866/PKU.WHXB202408004
7. [7]
  Xudong Lv , Tao Shao , Junyan Liu , Meng Ye , Shengwei Liu . Paired Electrochemical CO₂ Reduction and HCHO Oxidation for the Cost-Effective Production of Value-Added Chemicals. Acta Physico-Chimica Sinica, 2024, 40(5): 2305028-0. doi: 10.3866/PKU.WHXB202305028
8. [8]
  Jiapei Zou , Junyang Zhang , Xuming Wu , Cong Wei , Simin Fang , Yuxi Wang . A Comprehensive Experiment Based on Electrocatalytic Nitrate Reduction into Ammonia: Synthesis, Characterization, Performance Exploration, and Applicable Design of Copper-based Catalysts. University Chemistry, 2024, 39(6): 373-382. doi: 10.3866/PKU.DXHX202312081
9. [9]
  Zelong LIANG , Shijia QIN , Pengfei GUO , Hang XU , Bin ZHAO . Synthesis and electrocatalytic CO₂ reduction performance of metal-organic framework catalysts loaded with silver particles. Chinese Journal of Inorganic Chemistry, 2025, 41(1): 165-173. doi: 10.11862/CJIC.20240409
10. [10]
  Hui-Ying Chen , Hao-Lin Zhu , Pei-Qin Liao , Xiao-Ming Chen . Integration of Ru(Ⅱ)-Bipyridyl and Zinc(Ⅱ)-Porphyrin Moieties in a Metal-Organic Framework for Efficient Overall CO₂ Photoreduction. Acta Physico-Chimica Sinica, 2024, 40(4): 2306046-0. doi: 10.3866/PKU.WHXB202306046
11. [11]
  Wenlong LI , Xinyu JIA , Jie LING , Mengdan MA , Anning ZHOU . Photothermal catalytic CO₂ hydrogenation over a Mg-doped In₂O_3-x catalyst. Chinese Journal of Inorganic Chemistry, 2024, 40(5): 919-929. doi: 10.11862/CJIC.20230421
12. [12]
  Bingliang Li , Yuying Han , Dianyang Li , Dandan Liu , Wenbin Shang . One-Step Synthesis of Benorilate Guided by Green Chemistry Principles and in vivo Dynamic Evaluation. University Chemistry, 2024, 39(6): 342-349. doi: 10.3866/PKU.DXHX202311070
13. [13]
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14. [14]
  Lili Jiang , Shaoyu Zheng , Xuejiao Liu , Xiaomin Xie . Copper-Catalyzed Oxidative Coupling Reactions for the Synthesis of Aryl Sulfones: A Fundamental and Exploratory Experiment for Undergraduate Teaching. University Chemistry, 2025, 40(7): 267-276. doi: 10.12461/PKU.DXHX202408004
15. [15]
  Jiaojiao Yu , Bo Sun , Na Li , Cong Wen , Wei Li . Improvement of Classical Organic Experiment Based on the “Reverse-Step Optimization Method”: Taking Synthesis of Ethyl Acetate as an Example. University Chemistry, 2025, 40(3): 333-341. doi: 10.12461/PKU.DXHX202405177
16. [16]
  Mengyang LI , Hao XU , Zhonghao NIU , Chunhua GONG , Weihui ZHONG , Jingli XIE . Highly effective catalytic synthesis of β-amino alcohols by using viologen-polyoxometalate hybrid materials. Chinese Journal of Inorganic Chemistry, 2025, 41(7): 1294-1300. doi: 10.11862/CJIC.20250080
17. [17]
  Feifei Yang , Wei Zhou , Chaoran Yang , Tianyu Zhang , Yanqiang Huang . Enhanced Methanol Selectivity in CO₂ Hydrogenation by Decoration of K on MoS₂ Catalyst. Acta Physico-Chimica Sinica, 2024, 40(7): 2308017-0. doi: 10.3866/PKU.WHXB202308017
18. [18]
  Huijuan Liao , Yulin Xiao , Dong Xue , Mingyu Yang , Jianyang Dong . Synthesis of 1-Benzyl Isoquinoline via the Minisci Reaction. University Chemistry, 2025, 40(7): 294-299. doi: 10.12461/PKU.DXHX202409092
19. [19]
  Tong Zhou , Jun Li , Zitian Wen , Yitian Chen , Hailing Li , Zhonghong Gao , Wenyun Wang , Fang Liu , Qing Feng , Zhen Li , Jinyi Yang , Min Liu , Wei Qi . Experiment Improvement of “Redox Reaction and Electrode Potential” Based on the New Medical Concept. University Chemistry, 2024, 39(8): 276-281. doi: 10.3866/PKU.DXHX202401005
20. [20]
  Ji-Quan Liu , Huilin Guo , Ying Yang , Xiaohui Guo . Calculation and Discussion of Electrode Potentials in Redox Reactions of Water. University Chemistry, 2024, 39(8): 351-358. doi: 10.3866/PKU.DXHX202401031

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