Organic Process Research & Development,
Journal Year:
2024,
Volume and Issue:
28(11), P. 4034 - 4038
Published: Oct. 21, 2024
A
simple
and
widely
applicable
technique
to
avoid
precipitation-induced
clogging
in
continuous-flow
processes
involving
gas
liquid
reagents
(such
as
hydrogenations)
has
been
developed.
Management
of
solid
compounds
poses
one
the
largest
scale-up
risks
flow
manufacturing
pharmaceuticals
fine
chemicals.
As
noted
this
study,
with
limited
solubility
low-boiling
solvents
can
be
susceptible
precipitation
when
mixed
a
stream
standard
tee-mixer.
The
prescribed
technique,
whereby
is
prewetted
solvent
prior
contacting
feed
solution,
successfully
applied
both
lab
platforms
enhance
stable
(clog-free)
operating
run
time
synthesis
an
active
pharmaceutical
ingredient
(API)
intermediate
from
minutes
days.
Chemical Society Reviews,
Journal Year:
2023,
Volume and Issue:
52(21), P. 7305 - 7332
Published: Jan. 1, 2023
Electrochemical
hydrogenation
reactions
hold
the
promise
of
more
sustainable
production
routes
for
towards
bulk
and
fine
chemicals.
Their
broad
applicability,
reactor
concepts,
achieved
milestones
future
perspectives
are
described
herein.
Organic Process Research & Development,
Journal Year:
2024,
Volume and Issue:
28(5), P. 1327 - 1354
Published: March 14, 2024
The
effective
handling
of
solids
in
a
continuous
flow
process
is
one
the
biggest
perceived
challenges
remaining
for
modern
chemistry.
This
Review
aims
to
consider
some
processes
chemistries
involving
which
have
been
successfully
implemented.
Learnings
from
design
these
systems,
and
identification
common
blockers,
will
guide
generalized,
strategic
approach
drive
efficiency
future
batch-to-flow
development
challenging,
heterogeneous
systems.
Assorted
techniques
managing
continuous-flow
synthesis
be
presented
herein
through
series
case
studies,
broken
down
into
several
key
categories;
solubility
considerations,
setup
components
modularity,
applications
ultrasonication,
reactor
type
Grignard
reactions.
Angewandte Chemie International Edition,
Journal Year:
2023,
Volume and Issue:
63(11)
Published: Dec. 14, 2023
The
use
of
reactive
gaseous
reagents
for
the
production
active
pharmaceutical
ingredients
(APIs)
remains
a
scientific
challenge
due
to
safety
and
efficiency
limitations.
implementation
continuous-flow
reactors
has
resulted
in
rapid
development
gas-handling
technology
because
several
advantages
such
as
increased
interfacial
area,
improved
mass-
heat
transfer,
seamless
scale-up.
This
enables
shorter
more
atom-economic
synthesis
routes
compounds.
Herein,
we
provide
an
overview
literature
from
2016
onwards
well
gases
functionalization
APIs.
Organic Process Research & Development,
Journal Year:
2023,
Volume and Issue:
28(5), P. 1725 - 1733
Published: Dec. 14, 2023
Flow
reactors
with
enhanced
mixing
are
of
interest
to
the
pharmaceutical
industry
for
a
range
photochemical
applications.
Taylor–Couette
(vortex,
dynamically
mixed)
have
been
reported
intensified
and
used
heterogeneous
systems.
Our
workflow
has
previously
demonstrated
development
Wohl–Ziegler
process
scale-up
in
flow
using
plug
reactor
(PFR).
In
this
work,
20
mL
mixed
Autichem,
Ltd.
prototype
DART
(Taylor–Couette
reactor)
was
paired
four
custom
Kessil
PR160L
400
nm
lamps.
The
evaluated
as
500
g
option
bromination
ethyl
4-methylbenzoate.
Herein
we
describe
our
moving
from
Pacer
International
Photochemistry
LED
Illuminator
(HTS
system)
synthesis
4-(bromomethyl)benzoate
via
radical
process.
Reaction Chemistry & Engineering,
Journal Year:
2023,
Volume and Issue:
9(1), P. 132 - 138
Published: Sept. 29, 2023
The
combination
of
transient
flow
experiments
with
process
analytical
technology
(PAT)
enables
the
rapid
characterization
and
kinetic
modelling
a
complex
ketone
hydrogenation,
catalyzed
by
catalytic
static
mixers
(CSMs).
Organic Process Research & Development,
Journal Year:
2025,
Volume and Issue:
unknown
Published: Jan. 14, 2025
Fixed
bed
catalytic
reactors
are
commonly
used
for
hydrogenation
in
the
commodity
chemical
industry,
but
adoption
pharmaceutical
industry
has
been
limited
by
lack
of
available
catalyst
pellets
sizes
suitable
both
process
research
and
development
at
scales
1–50
g
substrate
per
experiment
also
to
manufacturing
metric
ton
scale.
Herein,
we
describe
an
approach
continuous
flow
using
cartridges
powdered
catalysts
(palladium
on
carbon
this
example)
enmeshed
expanded
poly(tetrafluoroethylene)
(ePTFE)
matrix.
Using
a
modular
design,
layers
supplemental
components
can
be
arranged
suit
specific
reaction
conditions,
desired
results,
throughput.
The
reactor
was
demonstrated
with
three
classes
reactions:
nitro
reduction,
debenzylation,
alkene
reduction.
All
substrates
could
achieve
high
or
full
conversion
after
optimization.
study
includes
longevity
experiments
understand
long-term
reliability
as
well
preliminary
results
scaling
up
larger
membrane
size.
make
technology
promising
scale-up
opportunities
same
design.
Organic Process Research & Development,
Journal Year:
2025,
Volume and Issue:
unknown
Published: Jan. 15, 2025
Catalytic
hydrogenations
are
key
processes
in
the
fine
chemical
and
pharmaceutical
industries,
but
development
of
such
is
challenging
due
to
aspects
as
catalyst
deactivation,
metal
leaching,
mass
transfer
limitations,
solubility
issues,
formation
side
products.
Processes
particularly
difficult
develop
when
a
substrate
large
molecule
containing
multiple
functional
groups.
These
difficulties
significant
obstacles
for
identification
robust
operating
conditions;
thus,
workflows
necessary
speed
up
timelines.
The
use
more
cost-effective
commercially
available
surrogate
an
alternative
strategy
find
optimized
conditions,
which
can
then
be
subsequently
validated
on
real
only
at
later
stage
development.
approach
we
apply
herein
designed
less
compound
while
minimizing
perceived
risk
failure
transferring
conditions
complex
molecule.
In
this
article,
our
workflow
catalytic
hydrogenolysis
glycopeptide
molecule,
Cbz-protected
(Cbz-GP),
packed
bed
reactor.
As
part
workflow,
robustness
screening
approach,
introduced
by
Collins
Glorius,
show
that
lysine
(Cbz-Lys),
presence
additives
mimic
secondary
groups
present
Cbz-GP
or
represent
residual
impurities
generated
upstream
synthesis
Cbz-GP.
data
Cbz-Lys
enabled
successful
deprotection
after
minor
modification.
Gratifyingly,
few
additional
experiments
were
using
GP
modify
achieve
>95%
conversion
under
mild
within
<10
s
contact
time
stable
performance
over
>6
h
operation
time.
