Organic Process Research & Development
Article
5
3
1
1
.96 (m, 1H), 5.20−5.17 (m, 1H), 5.16−5.14 (m, 3H), 3.78−
REFERENCES
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1
3
.76 (m, 3H), 3.39 (td, J = 6.3, 1.6 Hz, 2H). CNMR (CDCl ,
3
(
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00 MHz) δ 153.7, 147.9, 136.1, 126.5, 116.5, 116.5, 115.9,
+
12.6, 55.7, 35.3. LC−MS m/z: 165 (M + H ).
(
Optimization of reaction conditions was performed with the
Tetrahedron Lett. 1986, 27, 4945−4948.
neat, pale-yellow oil, 4-methoxy anisole, and 230−250, 260, and
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270 °C with 5, 10, or 15 min in RTU. The best conversion was
(
(
5) Schanche, J. S. Mol. Diversity 2003, 7, 293−300.
seen with 260 °C and 15 min in RTU. The 2-allyl-4-
methoxyphenol was synthesized pumping 1-(allyloxy)-4-
methoxybenzene neat (pale=yellow oil, 1.974 mL, 2.03 g,
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12.36 mmol, ρ = 1.0284 g/mL) through the CF-MAOS system
(
(
2
(
7) Larhed, M.; Hallberg, A. Drug Discovery Today 2001, 6, 406−416.
with 15 min RTU at 260 °C using a 3-mm reactor and
collecting for 42 min. The crude product (brown oil, 2.02 g,
mass balance = 99.5% recovered) was purified by silica flash
chromatography using 5−10% ethyl acetate in pentane as
eluent to give 10.50 mmol (1.725 g) in 85% isolated yield of 2-
allyl-4-methoxyphenol and an estimated throughput of 15.0
mmol/h (2.46 g/h).
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6
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(
̈
m, P.; Westman, J. Drug
2
-Methyl-1,4,4a,9a-tetrahydroanthracene-9,10-dione
16). The 2-methyl-1,4,4a,9a-tetrahydroanthracene-9,10-dione
16) was synthesized using isoprene (14) (29.99 mmol, 2.043
g) and 2,3-dihydronaphthalene-1,4-dione (15) (15.07 mmol,
.384 g) in NMP to a total volume of 14 mL, giving a
(
(
(
(
2
concentration of 15 of 1.07 M. The solution was connected to
the pump channel and 1 bar N was applied on the reservoir
flask. For isolated yield the reaction mixture was pumped
through the CF-MAOS system with 5 min residence time at
(
2
(
16) Jas, G.; Kirschning, A. Chem.Eur. J. 2003, 9, 5708−5723.
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190 °C using a 3-mm reactor. Sample for isolated yield was
collected for 20 min. The collected reaction mixture was filtered
through a Si plug with 10−20% ethyl acetate in isohexane and
concentrated under reduced pressure. The concentrate was
dissolved in MeCN and purified on RP-HPLC using 55−90%
MeCN in water with a gradient time of 7 min. Product-
containing fractions were combined and concentrated under
reduced pressure to give 1.574 mmol (0.356 g) in 52% isolated
(
20) Odell, L. R.; Lindh, J.; Gustafsson, T.; Larhed, M. Eur. J. Org.
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010, 14, 215−224.
(
(
2
(
23) Ceylan, S.; Coutable, L.; Wegner, J.; Kirschning, A. Chem.Eur.
1
yield and a throughput of 4.722 mmol/h (1.07 g/h). HNMR
J. 2011, 17, 1884−1893.
(
5
2
CDCl , 400 MHz) δ 8.08−8.03 (m, 2H), 7.78−7.72 (m, 2H),
3
(24) Ceylan, S.; Friese, C.; Lammel, C.; Mazac, K.; Kirschning, A.
Angew. Chem., Int. Ed. 2008, 47, 8950−8953.
(25) Gronnow, M. J.; White, R. J.; Clark, J. H.; Macquarrie, D. J. Org.
Process Res. Dev. 2005, 9, 516−518.
.43 (s, 1H), 3.45−3.39 (m, 1H), 3.37−3.31 (m, 1H), 2.56−
13
.42 (m, 2H), 2.28−2.10 (m, 2H), 1.70 (s, 3H). CNMR
CDCl , 100 MHz) δ 198.4, 198.1, 134.2, 134.1, 134.0, 131.8,
(
3
(
26) Gronnow, M. J.; White, R. J.; Clark, J. H.; Macquarrie, D. J. Org.
Process Res. Dev. 2007, 11, 293.
27) Moseley, J. D.; Woodman, E. K. Energy Fuels 2009, 23, 5438−
447.
(28) Moseley, J. D.; Kappe, C. O. Green Chem. 2011, 13, 794−806.
29) Cablewski, T.; Faux, A. F.; Strauss, C. R. J. Org. Chem. 1994, 59,
408−3412.
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1
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26.9, 126.8, 118.5, 47.1, 46.5, 29.0, 24.9, 23.4. GC−MS m/z:
+
26 (M ).
(
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ASSOCIATED CONTENT
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Supporting Information
Temperature profiles for solvents and reaction mixtures. LC- or
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GC chromatograms, and H and C NMR spectra for
8, 395−410.
32) Baxendale, I. R.; Pitts, M. R. Chim. Oggi 2006, 24, 41−45.
33) Baxendale, I. R.; Hayward, J. J.; Ley, S. V. Comb. Chem. High
AUTHOR INFORMATION
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Throughput Screening 2007, 10, 802−836.
(34) Wilson, N. S.; Sarko, C. R.; Roth, G. P. Org. Process Res. Dev.
2
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004, 8, 535−538.
35) Singh, B. K.; Kaval, N.; Tomar, S.; Van der Eycken, E.; Parmar,
V. S. Org. Process Res. Dev. 2008, 12, 468−474.
36) Baxendale, I. R.; Griffiths-Jones, C. M.; Ley, S. V.; Tranmer, G.
K. Chem.Eur. J. 2006, 12, 4407−4416.
37) Bagley, M. C.; Jenkins, R. L.; Lubinu, M. C.; Mason, C.; Wood,
R. J. Org. Chem. 2005, 70, 7003−7006.
38) Glasnov, T. N.; Vugts, D. J.; Koningstein, M. M.; Desai, B.;
*
Telephone: +46 18-471 4667.
Notes
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The authors declare no competing financial interest.
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ACKNOWLEDGMENTS
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We thank the Swedish Research Council (V.R.), Knut and Alice
Wallenberg’s foundation, and Wavecraft for financial support.
Fabian, W. M. F.; Orru, R. V. A.; Kappe, C. O. QSAR Comb. Sci. 2006,
25, 509−518.
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dx.doi.org/10.1021/op300003b | Org. Process Res. Dev. 2012, 16, 1053−1063