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Synlett 2011(10): 1375-1380  
DOI: 10.1055/s-0030-1260573
LETTER
© Georg Thieme Verlag Stuttgart ˙ New York

An Integrated Flow and Batch-Based Approach for the Synthesis of O-Methyl Siphonazole

Marcus Baumann, Ian R. Baxendale, Malte Brasholz, John J. Hayward, Steven V. Ley, Nikzad Nikbin
Innovative Technology Centre, Department of Chemistry, University of Cambridge, Lensfield Road, Cambridge CB2 1EW, UK
e-Mail: theitc@cam.ac.uk;
Further Information

Publication History

Received 21 February 2011
Publication Date:
23 May 2011 (online)

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Abstract

The bisoxazole containing natural product O-methyl siphonazole was assembled using a suite of microreactors via a flow-based approach in concert with traditional batch methods. The use of a toolbox of solid-supported scavengers and reagents to aid purification afforded the natural product in a total of nine steps.

Key words

oxazoles - Claisen condensation - flow chemistry - ­microreactors - solid-supported reagents

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Vapourtec© R2+/R4 system was used; website: www.vapourtec.co.uk.

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QP-SA and QP-DMA resins are commercially available from Johnson Matthey. Website: http://www.matthey.com/.

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An Omnifit column was used, www.omnifit.com.

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NMR Data
¹H NMR (600 MHz, CDCl3): δ = 2.64, 2.67 (2 s, 2 × 3 H, 18-H, 19-H), 3.92, 3.93 (2 s, 2 × 3 H, 20-H, 21-H), 4.03 (t, J = 5.8 Hz, 2 H, 1′-H), 4.41 (s, 2 H, 5-H), 5.06 (d, J = 10.3 Hz, 1 H, 5′-H), 5.18 (d, J = 17.0 Hz, 1 H, 5′-H), 5.73 (td, J = 5.8, 15.0 Hz, 1 H, 2′-H), 6.22 (dd, J = 10.3, 15.0 Hz, 1 H, 3′-H), 6.31 (td, J = 10.3, 17.0 Hz, 1 H, 4′-H), 6.75 (d, J = 16.4, 1 H, 10-H), 6.88 (d, J = 8.2 Hz, 1 H, 16-H), 7.00 (t, J = 5.8 Hz, 1 H, NH), 7.07 (d, J = 1.6 Hz, 1 H, 13-H), 7.09 (dd, J = 1.6, 8.2 Hz, 1 H, 17-H), 7.44 (d, J = 16.4 Hz, 1 H, 11-H) ppm. ¹³C NMR (150 MHz): δ = 11.7, 12.4 (2 q, C-18, C-19), 39.4 (t, C-5), 40.3 (t, C-1′), 55.9, 56.0 (2 q, C-20, C-21), 108.9 (d, C-13), 110.8 (d, C-10), 111.2 (d, C-16), 117.4 (t, C-5′), 121.5 (d, C-17), 128.1 (s, C-12), 129.45, 129.49 (2 d, C-2′, C-3′), 132.8 (s, C-2), 134.5 (s, C-7), 136.1 (d, C-4′), 137.3 (d, C-11), 149.3, 150.6 (2 s, C-14, C-15), 153.8 (s, C-3), 155.3 (s, C-8), 155.6 (s, C-4), 159.1 (s, C-9), 161.7 (s, C-1), 189.4 (s, C-6) ppm.