Biomedical Engineering Reference
In-Depth Information
O
NMe
3
CN
1.
Br
1. MnO
2
, PhMe
2.
OEt
OEt
cat. CH
3
CO
2
H
EtOH
N
BEMP
NCO
n
-Pr
N
OEt
n
-Pr
OEt
n
-Pr
N
Me
N
Me
N
H
N
O
N
Me
N
CN
O
NH
2
92%
90%
2.
Me
CN
O
n
-Pr
18
19
20
21
95% (2 steps)
1.
BEMP, EtOH
2. NH
3
, MeOH
95%
Me
N
Me
N
N
N
O
N
O
N
O
Me
O
O
O
Cl
N
HOBt
S
O
N
S
H
2
N
S
O
OH
OH
N
O
O
PyBrOP, DMF
81%
O
H
2
N
OH
OEt
OEt
n
-Pr
23
24
25
22
82%
NCO
H
2
N
OEt
OEt
O
μ
W, 120°C, 10 min
EtOH/NaOEt
n
-Pr
N
O
N
N
O
N
S
Me
N
N
S
O
HN
100%
O
N
O
N
Me
N
n
-Pr
Me
N
Sildenafil
27
O
26
Me
SCHEME 11.3
Synthesis of sildenafil (Viagra
27
).
hydrolysis in the presence of acetic anhydride, and bromination using an immobi-
lized perbromide.
Since alkaloids often provide interesting synthetic challenges, the prepa-
ration of (
þ
)-plicamine
41
using the new methods is particularly instructive
1. 1 M HBr, THF, 75°C
O
O
OMe
O
1.
NMe
3
NaCO
3
N
2.
SO
3
H
CH
2
Cl
2
, rt
,
Br
O
OH
Me
2
NCH
2
I, CH
2
Cl
2
, rt
SO
3
H
Ac
2
O, Toluene, 80°C
AcO
Ph
O
HO
AcO
2.
3. THF, rt
30
28
29
Ph
i-
Pr
N
HO
NH
2
CaCl
2
, MeOH, 0°C
i-
Pr
3.
NH Br
3
then
76%
81% (3 steps)
CH
2
Cl
2
, rt
NMe
3
BH
4
75% (3 steps)
OH
H
N
O
OH
Ph
31
O
1.
or
DMAP, MsCl, CH
2
Cl
2
, rt
1.
NMe
3
BH
3
CN
CH
2
Cl
2
, 5% AcOH, rt
NMe
3
NaCO
3
Pd(OH)
2
/C, H
2
, EtOAc
O
OH
PPh
2
, CBr
4
, CHCl
3
2.
3.
4.
2. HO(CH
2
)
6
OH, NaH
PhMe, 80°C
3. Al
2
O
3
, Pyridine, HCrO
3
Cl
CH
2
Cl
2
, rt
O
32
33
85%
SO
3
H
5. NH
3
/MeOH
92% (3 steps)
OH
N
HO
HO
Ph
O
(
R
)-Salmeterol
34
SCHEME 11.4
Synthesis of the bronchodilator (
R
)-salmeterol
34
.
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