3-Hydroxyazetidine hydrochloride

3-hydroxyazaecyclobutane hydrochloride is an azaecyclobutane compound that is an important intermediate in the synthesis of Brectinib, which is obtained through a multi-step reaction. Brectinib was approved by the European Union. The monotherapy or in combination with methotrexate for the treatment of adult patients with moderate to severe active rheumatoid arthritis with inadequate or intolerant relief from one or more antirheumatic drugs. It is also the first JAK inhibitor approved in the European Union for the treatment of rheumatoid arthritis.

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3-Hydroxyazetidine hydrochloride is an building block used in a recent synthesis of a fluoroquinolone antibiotic and a useful intermediate in the synthesis of polypeptides.

A solution of l-(diphenylmethyl)-3-hydroxy azetidine hydrochloride (11.8 g) in absolute ethanol (700 mL) was hydrogenated at room temperature over Pd(OH)2/C in a Parr shaker (4 atm). After 12 hr the catalyst was filtered off and the filtrate evaporated to dryness to give3-hydroxyazetidine hydrochloride (4.20 g, 94%).

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[1] Journal of Antibiotics, 2006, vol. 59, # 4, p. 241 - 247
[2] Journal of Medicinal Chemistry, 2008, vol. 51, # 15, p. 4601 - 4608
[3] Patent: WO2007/118830, 2007, A1. Location in patent: Page/Page column 91
[4] Patent: US2006/46991, 2006, A1. Location in patent: Page/Page column 57-58
[5] Patent: WO2006/21881, 2006, A2. Location in patent: Page/Page column 62; 63