Organic Process Research & Development
.7. Microfluidic Experiments. All microfluidic reactions
were carried out using a Chemtrix Labtrix S1 system, equipped
with 3223 or 3224 reactor chips.
Article
4
yield. The structure was confirmed by H NMR (Figure S5).
2
1
ASSOCIATED CONTENT
Supporting Information
4
.8. N-(2-Benzoyl-4-chlorophenyl)-2-halo-N-methyla-
cetamide (3). Solutions (100 mM) of 5-halo-2-
methylamino)benzophenone (1 equiv) and of haloacetyl
■
*
S
(
chloride (1 equiv) in toluene, ACN, DMF, or NMP were
prepared. In the DMF reaction screen, 500 mM solutions were
used; in the NMP reaction screens, 250 mM solutions of
benzophenone and 500 mM (2 equiv) chloroacetyl chloride
were used. A syringe was loaded with each of these two
solutions and positioned on the first two inlets of a 10 μL
Labtrix 3223 chip. A third syringe was loaded with toluene and
positioned on the third port of the same chip as a diluent. The
reaction was flowed with 30, 60, and 180 s residence times at
temperatures of 50, 100, and 150 °C. Samples were collected
and immediately analyzed by ESI-MS (1 μL of each sample was
diluted with 99 μL of ACN, then loaded into a glass
electrospray tip for analysis). Samples were saved and stored
at −20 °C.
Structure index, Figures S1−S5, Tables S1−S4 (PDF)
AUTHOR INFORMATION
■
*
*
ORCID
Author Contributions
†
H.S.E. and K.I. contributed equally.
Notes
4
.9. Diazepam (4) from N-(2-Benzoyl-4-chlorophenyl)-
The authors declare no competing financial interest.
2
-chloro-N-methylacetamide (3A). A 250 mM solution of
N-(2-benzoyl-4-chlorophenyl)-2-chloro-N-methylacetamide (1
equiv) was prepared. Syringes were loaded with the prepared
solution and with 7 N ammonia in methanol (7 equiv) and
positioned on the first two inlets of a 10 μL Labtrix 3223 chip.
A third syringe was loaded with NMP and positioned on the
third port of the same chip as a diluent. The reaction was
flowed with 30, 60, and 180 s residence times at temperatures
of 50, 100, and 150 °C. Samples were collected and
immediately analyzed by ESI-MS (1 μL of each sample was
diluted with 99 μL of ACN, then loaded into a glass
electrospray tip for analysis). Samples were saved and stored
at −20 °C.
ACKNOWLEDGMENTS
■
This work was supported by the Defense Advanced Projects
Agency of the United States of America and the National
Science Foundation (CHE-1307264).
REFERENCES
■
(
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.10. Diazepam (4) from 5-Halo-2-(methylamino)-
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(
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−20 °C.
4.11. Batch Synthesis of N-(2-Benzoyl-4-chlorophen-
yl)-2-chloro-N-methylacetamide (3A). Chloroacetyl chlor-
ide (0.39 mL, 4.9 mmol, 1 EQ) was added to a solution of 5-
chloro-2-(methylamino)benzophenone (1.2 g, 4.9 mmol) in
1
4
00 mL NMP (50 mM). The reaction was heated to 90 °C for
0 min. The solution was then concentrated in vacuo, and the
E
Org. Process Res. Dev. XXXX, XXX, XXX−XXX