Chemistry Reference
In-Depth Information
X
n
-BuLi
B(O
i
Pr)
3
XPhos precat
aq. KOH
Br
RT
2s - 10 min
60 °C
1min
60 °C
4-10 min
sonication
N
N
N
S
Me
N
N
Me
i-
Pr
Me
Me
Me
Me
OMe
Me
OMe
t
-Bu
t
-Bu
87%
83%
97%
96%
84%
Figure 13.8 Continuous flow setup for a lithiation-borylation-SMC sequence: mul-
tistep synthesis without intermediate purification.
groups, e.g. esters.
33
Crucial for success was a very fast lithiation (a few
milliseconds) followed by immediate quenching of the reaction stream with
B(OMe)
3
.
However, in most instances, impurities and excess of reagents are detri-
mental for follow-up catalytic reactions. In such cases, an in-line purification
is mandatory for success of the multistep flow protocol. One approach in-
volves the use of immobilized scavengers that are loaded into a micro
packed-bed reactor. This strategy was used for the synthesis of a key inter-
mediate of the fungicide boscalid (Figure 13.9).
34
In the first step, an SMC
reaction was carried out with 0.25 mol% Pd(PPh
3
)
4
and superheating of the
reaction mixture. The presence of a homogeneous Pd catalyst in the
hydrogenation step resulted in a significant amount of overreduced product.
Therefore, an intermediate scavenging step was required; QuadraPure TU
(a thiourea-based scavenger) was used to remove the remaining dissolved
palladium. Next, the purified reaction stream was merged with hydrogen
and directed over a Pt/C packed bed to permit the hydrogenation of the nitro
group. The target compound was obtained in 77% overall yield.
Another way of purifying the reaction stream is to make use of unit
operations. In contrast to the scavenging strategy, which requires replace-
ment of the cartridges after saturation, no interruption of the continuous
operation is required with unit operations to achieve the purification. An
example of this principle is illustrated in Figure 13.10.
35
In the first step,
phenols were reacted with triflic anhydride to yield the corresponding
Search WWH ::
Custom Search