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In-Depth Information
Pd(OAc)
2
(5 mol%)
TBAB (5 mol%), KOAc (2 equiv)
X
X
DMA/H
2
O(10:1)
90 °C, 3-6h
ultrasound
Br
X=N,O
O
O
O
O
OMe
NO
2
CHO
O
89%
90%
92%
94%
MeO
N
N
O
O
2
N
NTs
OMe O
77%
77%
91%
98%
Figure 13.26 Continuous flow direct arylation to form heterocyclic biaryls.
CF
3
CO
2
K, CuI
EtOAc
pyridine, NMP
I
CF
3
R
R
200-210 °C
trif luoromethylation
CF
3
CF
3
CF
3
Me
O
n
Bu
N
CF
3
N
Bn
Et
2
NO
2
S
N
CF
3
Bn
N
N
93%
79%
77%
83%
64%
Figure 13.27 Copper-mediated trifluoromethylation at elevated temperature in con-
tinuous flow.
13.4.12 Copper-Mediated Trifluoromethylation in Flow
The insertion of trifluoromethyl groups into drug compounds is an
important strategy to improve their chemical and physical properties.
A copper-mediated process was developed for the rapid trifluoromethylation
in continuous flow using CF
3
CO
2
KasaCF
3
source (Figure 13.27).
57
The re-
agents were introduced into a stainless-steel capillary microreactor which was
heated to 200 1C. At this temperature, copper-mediated trifluoromethylation
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