Chemistry:Broxaterol
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Broxaterol is a β2 adrenoreceptor agonist.[1] It is part of a class of drugs that affect the smooth muscle receptors in the body, often in use cases for respiratory disease that respond to this type of treatment.
Synthesis
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The 1,3-dipolar cycloaddition between bromonitrile oxide, produced in situ from dibromoformaldoxime, and 3-butyn-2-one gives a mixture of isoxazoles, mainly the isomer shown required for broxaterol. Selective α-bromination of the acetyl group with pyridinium tribromide gives a bromoketone whose carbonyl group is reduced with sodium borohydride to produce a bromoethanol derivative. Treatment of this with tert-butylamine yields broxaterol.[2][3][4][5]
References
- ↑ "Effect of a beta 2-agonist (broxaterol) on respiratory muscle strength and endurance in patients with COPD with irreversible airway obstruction". Chest 101 (1): 133–40. January 1992. doi:10.1378/chest.101.1.133. PMID 1345900. http://www.chestjournal.org/cgi/pmidlookup?view=long&pmid=1345900.
- ↑ Davide Della Bella and Dario Chiarino, "1-(3-Bromo-isoxazol-5-yl)-2-tert.butylaminoethanol", US patent 4276299, issued 1981-06-30, assigned to Zambon SpA
- ↑ De Amici, Marco; De Micheli, Carlo; Carrea, Giacomo; Spezia, Sandro (1989). "Chemoenzymatic synthesis of chiral isoxazole derivatives". The Journal of Organic Chemistry 54 (11): 2646–2650. doi:10.1021/jo00272a037.
- ↑ Rohloff, John C.; Robinson, James; Gardner, John O. (1992). "Bromonitrile oxide [3+2] cycloadditions in water". Tetrahedron Letters 33 (22): 3113–3116. doi:10.1016/S0040-4039(00)79827-3.
- ↑ Battilocchio, Claudio; Bosica, Francesco; Rowe, Sam M. et al. (2017). "Continuous Preparation and Use of Dibromoformaldoxime as a Reactive Intermediate for the Synthesis of 3-Bromoisoxazolines". Organic Process Research & Development 21 (10): 1588–1594. doi:10.1021/acs.oprd.7b00229.
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