Biomedical Engineering Reference
In-Depth Information
O
O
O
P
OMe
N
3
(2 equiv)
Ph
H
Me
OMe
100°C, 30 min
N
2
NH
2
SO
3
H
NMe
2
R
121
(2 equiv)
in MeCN
70°C
t-
BuOK in MeOH
(1.2 equiv)
S
N
N
H
NH
2
N
NMe
2
•
CuI
N
100 psi bpr
R
122
(62-69% by crystallisation)
2 examples
SCHEME 11.37
Synthesis of triazoles
122
using the Bestmann-Ohira reagent
121
.
O
O
Me
Me
P
OMe
Me
OMe
N
N
2
O
N
3
SO
3
Me
Me
121
MeCN
S
F
100°C, 48 min
(2 equiv)
60°C
100 psi bpr
N
H
NH
2
OH
NMe
2
•
CuI
Ph
(2 equiv)
t-
BuOK in MeOH
(1.2 equiv)
N
N
N
SO
3
H
NMe
2
NH
2
Ph
100 psi bpr
70°C
123
F
(55% by crystallisation)
SCHEME 11.38
Synthesis of triazole
123
from the corresponding alcohol using the
Bestmann-Ohira reagent
121
.
was used in a multistep sequence
involving the transformation of alcohols to the corresponding triazoles
(Scheme 11.38). In this work, a benzyl alcohol mixed with
Finally, the Bestmann-Ohira reagent
121
and an azide were
passed through a column of immobilized TEMPO to selectively oxidize the alcohol to
the aldehyde. Next, potassium butoxide in methanol was introduced to the flow line
that then progresses through a series of scavengers and reaction cartridges to finally
afford the triazole
121
123
in high purity and 55% yield after crystallization.
11.4.6. 3-Nitropyrrolidine Building Blocks
Another useful functionalized heterocycle for potential incorporation into medici-
nally relevant products are the 3-nitropyrrolidines [44]. The compounds can be
prepared using TFA or a fluoride monolith to facilitate dipole formation, followed by
dipolar cycloaddition with alkenes. In an early example, a stream of the nitroalkene
with TFAwas combined with a second stream containing the
N
-(methoxymethyl)-
N
-
(trimethylsilyl)benzylamine
coupling partner. The combined flow stream was
heated between 60 and 120
C for 30-90min, depending on the substrate, and then
124
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