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

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

19 Citations (Scopus)

415 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

Funding

This project was funded by the Horizon 2020: Marie Skolodowska-Curie Individual Fellowship awarded by Dr. Marc Escribà Gelonch under Grant Agreement Number 659233. The authors also acknowledge Celina Rodrigues de Oliveira for her support as well as the funding granted by the Erasmus program and the mobility program of Graz University of Technology to H.G.-W.

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10.1021/acs.oprd.7b00351

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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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