Cabozantinib
(CBT)
is
a
small-molecule
pharmaceutical
approved
for
the
treatment
of
medullary
thyroid
cancer,
advanced
renal
cell
carcinoma,
and
hepatocellular
carcinoma.
The
two-step
amidation
starting
with
1,1-cyclopropanedicarboxylic
acid
(CBT-1)
large-scale
synthetic
route
CBT,
but
existing
processes
suffered
from
highly
toxic
reagents,
low
yields,
long
reaction
times.
In
this
work,
cascaded
flow
process
was
developed
to
synthesize
CBT
in
microreactor.
first
step,
CDI
determined
as
coupling
reagent
generate
1-(4-fluorophenylaminoformyl)
cyclopropane
carboxylic
(CBT-3)
yield
97.5%
after
optimizing
operating
conditions.
Then,
EDCI/HOBt
were
screened
reagents
obtain
second
possible
paths
intrinsic
kinetics
revealed
result
indicated
that
formation
ion
pairs
between
CBT-3
EDCI
rate-determining
step
whole
process.
end,
two
reactions
microreactor,
synthesized
total
96.1%
35
min.
scale-up
microchemical
system
showed
productivity
can
achieve
about
5.3
g/h.
Compared
processes,
milder
reagents/conditions
used,
innovative
approach
continuous
synthesis
provide
an
efficient
alternative
method
production
CBT.
The Canadian Journal of Chemical Engineering,
Journal Year:
2025,
Volume and Issue:
unknown
Published: April 24, 2025
Abstract
Monosubstituted
symmetrical
dialkoxysilanes,
intermediates
in
the
production
of
numerous
well‐known
materials,
present
challenges
for
selective
monosubstitution
due
to
presence
two
alkoxy
groups
similar
chemical
environments.
Notably,
kinetic
studies
on
this
phenomenon
have
not
been
documented.
In
addressing
knowledge
gap,
we
developed
a
continuous
flow
system
reaction
kinetics
between
diethoxydimethylsilane
and
vinyl
magnesium
chloride,
enhancing
our
understanding
these
reactions.
We
initially
analyzed
order,
pre
‐exponential
factors,
activation
energies
systematically.
The
investigation
revealed
that
partial
order
was
first‐order,
chloride
also
overall
second‐order.
energy
main
39.21
kJ/mol,
side
59.72
kJ/mol.
Therefore,
precise
control
conditions
is
essential
improving
yield.
This
identified
potential
mechanism,
which
later
confirmed
through
series
experiments.
These
experiments
accurately
determined
applicable
concentration
temperature
ranges
model.
Further,
simulations
model
assessed
influences
molar
ratios
selectivity,
aiming
achieve
controlled
outcomes.
study
provides
new
insights
into
Grignard
reagents
with
dialkoxysilanes
offers
valuable
guidance
optimizing
industrial
applications.
demonstrates
laminar
reactor.
Compared
traditional
batch
processes,
reactor
achieved
milder
higher
reaching
99.5%
selectivity
97.9%
yield
simulations.
ACS Sustainable Chemistry & Engineering,
Journal Year:
2024,
Volume and Issue:
12(20), P. 7913 - 7923
Published: May 9, 2024
Capsaicin
and
its
derivatives
are
special
alkaloids
responsible
for
the
pungency
of
spicy
pepper
fruits
mainly
used
in
pharmaceutical,
food,
cosmetic
industries.
Until
now,
only
batch
syntheses
capsaicin
some
analogues
have
been
described;
drawbacks,
such
as
long
reaction
time,
variable
yields,
chemical
waste
emission,
still
challenge
organic
chemists
to
make
progress
environmentally
friendly
synthesis.
In
this
study,
we
developed
first
flow
synthesis
based
on
three
steps,
oxime
formation
benzaldehydes,
reduction
oximes,
N-acylation
benzylamines
with
carboxylic
acids.
Each
continuous
steps
was
optimized
by
a
model
reaction,
after
that,
were
coupled
semicontinuous
system.
Our
method
is
safer,
faster,
more
atom-efficient,
process
than
approaches
described
literature;
furthermore,
our
accordance
seven
12
principles
green
chemistry.
addition,
3D
printed
reactors
also
nonivamide
demonstrate
an
alternative
cheaper
way
Chemical Engineering Journal,
Journal Year:
2024,
Volume and Issue:
493, P. 152159 - 152159
Published: May 11, 2024
Diphenhydramine
is
a
first-generation
antihistamine
that
available
over-the-counter
to
treat
maladies
such
as
allergic
reactions
and
insomnia.
Despite
its
ubiquity
in
society
high
demand,
the
kinetics
for
either
step
of
diphenhydramine
synthesis
have
not
been
explored
detail.
In
this
work,
first
step,
methodology
has
devised
obtain
from
heterogeneous
halogenation
benzhydrol
with
hydrochloric
acid
batch
reactor
equipped
in-situ
Raman
probe
further
verified
ex-situ
low-field
NMR
spectroscopy.
For
second
etherification
using
microfluidic
flow
at-line
spectroscopy
variety
solvents.
Arrhenius
Eyring
parameters
are
determined
Step
2.
We
find
reaction
performance
well
correlated
acceptor
number
solvent
indicating
Lewis
acidity
plays
significant
role
overall
Reaction Chemistry & Engineering,
Journal Year:
2024,
Volume and Issue:
9(9), P. 2411 - 2418
Published: Jan. 1, 2024
Superior
selectivity
and
yield
for
monoacylated
diamines;
green
reagents
relatively
benign
by-products;
efficient
processes
with
short
residence
time
are
discussed.
