Continuous-Flow In-Line Solvent-Swap Crystallization of Vitamin D3

Marc Escribà-Gelonch; Volker Hessel; Manuel C. Maier; Timothy Noël; Maria Fernanda Neira D'Angelo; Heidrun Gruber-Woelfler

doi:10.1021/acs.oprd.7b00351

Continuous-Flow In-Line Solvent-Swap Crystallization of Vitamin D₃

Marc Escribà-Gelonch, Volker Hessel, Manuel C. Maier, Timothy Noël, Maria Fernanda Neira D'Angelo, Heidrun Gruber-Woelfler

Micro Flow Chemistry and Synthetic Methodology

Research output: Contribution to journal › Article › Academic › peer-review

12 Citations (Scopus)

187 Downloads (Pure)

Abstract

A continuous tandem in-line evaporation-crystallization is presented. The process includes an in-line solvent-swap step, suitable to be coupled to a capillary based cooler. As a proof of concept, this setup is tested in a direct in-line acetonitrile mediated crystallization of Vitamin D₃. This configuration is suitable to be coupled to a new end-to-end continuous microflow synthesis of Vitamin D₃. By this procedure, vitamin particles can be crystallized in continuous flow and isolated using an in-line continuous filtration step. In one run in just 1 min of cooling time, ∼50% (w/w) crystals of Vitamin D₃ are directly obtained. Furthermore, the polymorphic form as well as crystals shape and size properties are described in this paper.

Original language	English
Pages (from-to)	178-189
Number of pages	12
Journal	Organic Process Research & Development
Volume	22
Issue number	2
DOIs	https://doi.org/10.1021/acs.oprd.7b00351
Publication status	Published - 1 Feb 2018

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abstract = "A continuous tandem in-line evaporation-crystallization is presented. The process includes an in-line solvent-swap step, suitable to be coupled to a capillary based cooler. As a proof of concept, this setup is tested in a direct in-line acetonitrile mediated crystallization of Vitamin D3. This configuration is suitable to be coupled to a new end-to-end continuous microflow synthesis of Vitamin D3. By this procedure, vitamin particles can be crystallized in continuous flow and isolated using an in-line continuous filtration step. In one run in just 1 min of cooling time, ∼50% (w/w) crystals of Vitamin D3 are directly obtained. Furthermore, the polymorphic form as well as crystals shape and size properties are described in this paper.",

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AB - A continuous tandem in-line evaporation-crystallization is presented. The process includes an in-line solvent-swap step, suitable to be coupled to a capillary based cooler. As a proof of concept, this setup is tested in a direct in-line acetonitrile mediated crystallization of Vitamin D3. This configuration is suitable to be coupled to a new end-to-end continuous microflow synthesis of Vitamin D3. By this procedure, vitamin particles can be crystallized in continuous flow and isolated using an in-line continuous filtration step. In one run in just 1 min of cooling time, ∼50% (w/w) crystals of Vitamin D3 are directly obtained. Furthermore, the polymorphic form as well as crystals shape and size properties are described in this paper.

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Continuous-Flow In-Line Solvent-Swap Crystallization of Vitamin D₃

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