A Scalable, Chromatography-Free Synthesis of Benzotetramisole

Abstract

The scalable, chromatography-free synthesis of the chiral isothiourea benzotetramisole (BTM) in two steps from commercially available materials is presented. A detailed procedure for the synthesis of both enantiomers and the racemate on ca. 10 gram scale is disclosed.

Key words

isothiourea - Lewis base catalysis - asymmetric catalysis - kinetic resolution - rearrangement - benzotetramisole

• References

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• 19 See experimental for details.
• 20 The site of N-mesylation was determined by ¹H-¹⁵N HMBC spectroscopy, supported by DFT calculations for the ¹⁵N chemical shifts. See Supporting Information for details.
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• 24 GC analysis indicated >95% conversion of 2-chlorobenzothiazole against o-dichlorobenzene as the internal standard. Approximately 200 μL samples of the reaction mixture at t = 0 and 24 h were taken and diluted to ~1.5 mL in CH₂Cl₂ for analysis.