Organic Process Research & Development
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in an oil bath (80 °C). A solution of MsOH (85%) in DME
(flow rate: 4.000 mL/h) and the binary solution of 3a (0.20 M)
and TBAA (0.27 M) in DME (flow rate: 2.000 mL/h) were fed
into the system by syringe pumps. After a steady state was
reached (15 min), the discharge was quenched and collected
for 2 h in a glass vessel with ice in it. The product solution was
poured into a beaker containing crushed ice and neutralized
with ammonia solution until pH = 9 then extracted with
CH2Cl2. The combined organic phase was dried over Na2SO4,
filtered, and concentrated. The resulting crude product was
purified by flash chromatography on silica gel with hexane and
AcOEt as eluent to afford 3b (99 mg, 92% yield).
Scale-up for the Schmidt Reaction by Prolonging the
Operation Time. Acetanilide (3b): Using the same micro-
reactor system as above, a solution of MsOH (85%) in DME
(flow rate: 4.000 mL/h) (for details of MsOH feeding, see
Supporting Information) and the binary solution of 3a (0.20
M) and TBAA (0.27 M) in DME (flow rate: 2.000 mL/h) were
fed into the system. After a steady state was reached (15 min),
the discharge was quenched and collected (20 h) in a glass
vessel with ice in it. The same workup and purification was
performed to afford 3b (983 mg, 91% yield).
Scale-up for the Schmidt Reaction by Prolonging the
Operation Time and Doubling the Substrate Concen-
tration. Acetanilide (3b): Using the same microreactor system
as above, a solution of MsOH (85%) in DME (flow rate: 4.000
mL/h) and the binary solution of 3a (0.40 M) and TBAA (0.54
M) in DME (flow rate: 2.000 mL/h) were fed into the system.
After a steady state was reached (15 min), the discharge was
quenched and collected (20 h) in a glass vessel with ice in it.
The same workup and purification was performed to afford 3b
(1.946 g, 90% yield).
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ASSOCIATED CONTENT
* Supporting Information
■
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4246−4249. (b) Chernyak, N.; Buchwald, S. L. J. Am. Chem. Soc. 2012,
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2012, 16 (10), 1669−1672.
S
Detailed experimental procedures and compounds character-
ization data for all described compounds. This material is
(18) Baumann, M.; Baxendale, I. R.; Ley, S. V.; Nikbin, N.; Smith, C.
D. Org. Biomol. Chem. 2008, 6, 1587−1593.
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AUTHOR INFORMATION
Corresponding Author
21-6564-2261.
■
(20) McPake, C. B.; Sandford, G. Org. Process Res. Dev. 2012, 16 (5),
844−851.
(21) (a) Liu, B.; Fan, Y.; Lv, X.; Liu, X.; Yang, Y.; Jia, Y. Org. Process
Res. Dev. 2013, 17 (1), 133−137. (b) Sedelmeier, J.; Lima, F.; Litzler,
A.; Martin, B.; Venturoni, F. Org. Lett. 2013, 15 (21), 5546−5549.
(22) Painter, T. O.; Thornton, P. D.; Orestano, M.; Santini, C.;
Notes
The authors declare no competing financial interest.
Organ, M. G.; Aube,
́
J. Chem.Eur. J. 2011, 17, 9595−9598.
ACKNOWLEDGMENTS
■
This work was financially supported by the National Basic
Research Program of China (973 Program) No.
2007CB714504.
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