Chemistry Reference
In-Depth Information
ever, has a short in vivo half-life in humans of 2 h. This can be prolonged by its
specific derivatization. The intermediate 920 was prepared in 70% yield by cyclo-
carbonylation of the vicinal diol 919 using CDI [660].
O
O
NaHMDS
THF
O
920
O
O
919
H
70 %
O
-35°C
OH
O
CDI
O
OR
1
O
OR
1
rt, 15 min
O
OR
2
O
OR
2
N
O
AcO
R
2
=
R
1
=
OCO
2
Bn
OMe
O
Typical procedure. 2
0
-Acetyl-4
00
-O-benzyloxycarbonyl-6-O-methyl-erythromycin A 11,12-
carbonate 920 [660]:
A solution of diol 919 (0.51 g, 0.55 mmol) in THF (10 mL)
at
35
C was treated with sodium bis(trimethylsilyl)amide in THF (0.7 mL of a
0.84 m solution; 0.6 mmol). After 10 min, a solution of CDI (0.33 g, 2.0 mmol) in
THF (5 mL) was added. The reaction mixture was allowed to warm to room tem-
perature and kept at this temperature for 15 min. It was then cooled to 0-5
C (ice/
water bath) and 0.5 m NaH
2
PO
4
solution was added. The aqueous layer was ex-
tracted twice with ethyl acetate. The combined organic layers were dried (magne-
sium sulfate) and concentrated to a yellow oil. The residue was purified by flash
chromatography eluting with acetonitrile/dichloromethane/concentrated ammo-
nium hydroxide (1:1:0.01) to afford 370 mg (70%) of carbonate 920; mp 248-
250
C; IR (CDCl
3
): n
max
1800 cm
1
O).
The heterocyclic systems perhydro-1,5,2-dioxazin-3,6-diones 922 are synthesized
in yields of 68-92% by cyclocarbonylation of hydroxamic acids 921 with CDI in
very short reaction times of 30-60 s [661]. Prolonged reaction times (60 min) and
an increased reaction temperature (40
C) lead to further reactions forming either
linear carbonates 923 or phenylglyoxylamides 924, depending on the nature of R
1
and R
2
.
¼
(cyclic carbonate C
b
General procedure. Preparation of perhydro-1,5,2-dioxazine-3,6-diones 922 [661]: A so-
lution of CDI (10 mmol) in dry dichloromethane (50 mL) is added to a suspension
of 921 (10 mmol) in dry dichloromethane (100 mL). After 30-60 s (!), the reaction
mixture is extracted with ice-cold 3 n HCl. The organic layer is dried over magne-
sium sulfate and filtered through silica gel. The solvent is evaporated, the residue
