Development of a continuous flow synthesis of propranolol: tackling a competitive side reaction

Angelis, Sonia De; Celestini, Paolo; Purgatorio, Rosa; Degennaro, Leonardo; Rebuzzini, Gabriele; Luisi, Renzo; Carlucci, Claudia

doi:10.1007/s41981-019-00047-8

Cited by 7 publications

(8 citation statements)

References 22 publications

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“…[ 3 , 4 ] and in synthetic methods requiring a high temperature and pressure [ 5 , 6 , 7 ], as well. In addition, it enables cleaner reaction profiles with better product–side-product ratios, and reaction pathways that could hardly be realized in batch processes (e.g., use of highly reactive peptidyl donors) [ 8 , 9 , 10 ]. Moreover, CF techniques are suitable for multistep [ 11 , 12 , 13 , 14 ] and automated synthetic processes, which is a rapidly growing field in modern organic chemistry [ 15 , 16 , 17 ].…”

Section: Introductionmentioning

confidence: 99%

Continuous-Flow Synthesis of Thioureas, Enabled by Aqueous Polysulfide Solution

et al. 2021

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We have developed the continuous-flow synthesis of thioureas in a multicomponent reaction starting from isocyanides, amidines, or amines and sulfur. The aqueous polysulfide solution enabled the application of sulfur under homogeneous and mild conditions. The crystallized products were isolated by simple filtration after the removal of the co-solvent, and the sulfur retained in the mother liquid. Presenting a wide range of thioureas synthesized by this procedure confirms the utility of the convenient continuous-flow application of sulfur.

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Section: Introductionmentioning

confidence: 99%

Continuous-Flow Synthesis of Thioureas, Enabled by Aqueous Polysulfide Solution

et al. 2021

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“…A schematic outline of the reactor used in this study is shown in Figure 1. reaction routes that would otherwise only be feasible under regular batch conditions, e.g., higher temperature and pressure than can be used under safe conditions [47][48][49][50][51][52][53][54][55][56][57]. Whilst acetonitrile is a common solvent and is generally used in various fields of chemistry as eluent [41] and polar aprotic organic solvent [58], it is rarely used as reagent in organic chemistry.…”

Section: Resultsmentioning

confidence: 99%

“…Furthermore, more efficient and selective reaction can be carried out in continuous systems than in regular batch operations [41][42][43][44][45][46]. Additionally, flow reaction conditions can enable reaction routes that would otherwise only be feasible under regular batch conditions, e.g., higher temperature and pressure than can be used under safe conditions [47][48][49][50][51][52][53][54][55][56][57].…”

Section: Introductionmentioning

confidence: 99%

N-Acetylation of Amines in Continuous-Flow with Acetonitrile—No Need for Hazardous and Toxic Carboxylic Acid Derivatives

2020

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A continuous-flow acetylation reaction was developed, applying cheap and safe reagent, acetonitrile as acetylation agent and alumina as catalyst. The method developed utilizes milder reagent than those used conventionally. The reaction was tested on various aromatic and aliphatic amines with good conversion. The catalyst showed excellent reusability and a scale-up was also carried out. Furthermore, a drug substance (paracetamol) was also synthesized with good conversion and yield.

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“…1 H NMR (300 MHz, CDCl 3 ) δ 7.36−7.24 (m, 5H), 4.49 (s, 2H), 3.53 (t, J = 6.6 Hz, 2H), 2.67 (t, J = 6.6 Hz, 2H), 2.41 (s, 3H), 1.79 (q, J = 6.6 Hz, 2H), 1.32 (br s, 1H); 13 C NMR (75 MHz, CDCl 3 ) δ 138.6, 128.4, 127.6, 127.5, 72.9, 68.9, 49. 3-(Methylamino)-1-phenylpropan-1-ol (22). The title compound was prepared according to the general procedure from 3-hydroxy-3-phenylpropyl methanesulfonate (S3) (288 mg, 1.25 mmol, 0.25 M in MeOH or in MeCN).…”

Section: ■ Conclusionmentioning

confidence: 99%

Convenient Continuous Flow Synthesis of N-Methyl Secondary Amines from Alkyl Mesylates and Epoxides

Mathieu

Patel

Lebel

2020

Org. Process Res. Dev.

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The first continuous flow process was developed to synthesize N-methyl secondary amines from alkyl mesylates and epoxides via a nucleophilic substitution using aqueous methylamine. A variety of N-methyl secondary amines were produced in good to excellent yields, including a number of bioactive compounds or their precursors. Up to 10.6 g (88% yield) of an N-methyl secondary amine was produced in 140 min process time. The amination procedure included an in-line workup, and the starting mesylate material was also produced in continuous flow from the corresponding alcohol. Finally, an in-line process combining the mesylate synthesis and nucleophilic substitution was developed.

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Development of a continuous flow synthesis of propranolol: tackling a competitive side reaction

Cited by 7 publications

References 22 publications

Continuous-Flow Synthesis of Thioureas, Enabled by Aqueous Polysulfide Solution

Continuous-Flow Synthesis of Thioureas, Enabled by Aqueous Polysulfide Solution

N-Acetylation of Amines in Continuous-Flow with Acetonitrile—No Need for Hazardous and Toxic Carboxylic Acid Derivatives

Convenient Continuous Flow Synthesis of N-Methyl Secondary Amines from Alkyl Mesylates and Epoxides

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