An Efficient, Scalable Process for Benzphetamine Hydrochloride

Abstract

Commercial manufacturing of benzphetamine hydrochloride along with its impurity profiling is disclosed. Deoxygenation of pseudoephedrine is reported with ∼100% retention by shielding the amine group as its tert-butyl carbamate, which is very straightforward to eliminate at the end. Four unknown process-related impurities are isolated from the samples of final API and characterized on the basis of their NMR and mass spectral analysis. Structures of the isolated impurities are confirmed by independent syntheses and coinjecting with the isolated one.

Chemoenzymatic Synthesis of Selegiline: An Imine Reductase-Catalyzed Approach

“…Racemic approaches [ 10 , 11 ], chiral pool starting materials, asymmetric hydrogenation, classical/kinetic resolutions [ 12 , 13 ], regioselective aziridine ring openings with organocuprates [ 14 ], OsO 4 -catalyzed asymmetric dihydroxylations [ 15 ], and proline based functionalization of aldehydes [ 16 ] are the most reported synthetic strategies of ( R )-selegiline. In 2014, Pramanik and co-workers reported a deoxygenation of the pseudoephedrine approach to prepare ( R )-selegiline ( Figure 2 A) [ 17 ]. In the following year, Sudalai and co-workers employed Evans’ electrophilic azidation of chiral imide enolates as the key chiral-inducing step to synthesize ( R )-selegiline in high enantioselectivity (97%, R ) ( Figure 2 A) [ 18 ].…”

“…Herein, we develo an engineered IR36-M5 catalyzed reductive amination approach to access the key in mediate (R)-desmethylselegiline, 1a (Figure 2B). Prior synthesis and our synthetic strategy, 2014 [17], 2015 [18], 2021 [19].…”

“…Organic synthesis using biocatalysts has become a research hotspot in green chem try. Biocatalysis mediated by biological enzymes has the advantages that reactions generally carried out at an ambient temperature, atmospheric pressure, and near-neu conditions, with high catalytic efficiency, conversion, and stereo-and regioselectiv Asymmetric reductive amination is one of the most direct and efficient strategie Prior synthesis and our synthetic strategy, 2014 [17], 2015 [18], 2021 [19].…”

Safety Case Study. Intrinsic Instability of Concentrated Solutions of Alcoholic Hydrogen Chloride: Potential Hazards Associated with Methanol

“…2 In the field of protecting groups, hydrogen chloride in ethyl acetate is a valuable tool to remove the Boc group, for example. 3 Hydrogen chloride in alcohols can be prepared by following various procedures to generate HCl in situ, such as addition of chlorotrimethylsilane to various alcohols 4 or addition of acyl chloride to ethanol, 5 or by bubbling of gaseous HCl in alcohols. 6 Herein, after experiencing an incident in the laboratory with this latter procedure, we wish to give insight into the stability and safety concerns of methanolic hydrochloride.…”

“…Examples of esterification of carboxylic acids are also described . In the field of protecting groups, hydrogen chloride in ethyl acetate is a valuable tool to remove the Boc group, for example . Hydrogen chloride in alcohols can be prepared by following various procedures to generate HCl in situ, such as addition of chlorotrimethylsilane to various alcohols or addition of acyl chloride to ethanol, or by bubbling of gaseous HCl in alcohols .…”