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DOI: 10.1055/s-0030-1260573
An Integrated Flow and Batch-Based Approach for the Synthesis of O-Methyl Siphonazole
Publication History
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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References and Notes
Vapourtec© R2+/R4 system was used; website: www.vapourtec.co.uk.
13QP-SA and QP-DMA resins are commercially available from Johnson Matthey. Website: http://www.matthey.com/.
19An Omnifit column was used, www.omnifit.com.
24
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.