Chemistry Reference
In-Depth Information
O
O
Cl
COCl
2
97 % 1
pure, 12 h
- 20° to 0°C
OH
Cl
(Cl
3
CO)
2
CO
Cl
O
O
pyridine
THF or CH
2
Cl
2
rt, 15 min
1
90 %
2
Benzyl alcohol does not react with triphosgene at the low temperatures used in the
above example in the absence of a base. On reacting benzyl alcohol with triphos-
gene at room temperature in the presence of pyridine, only benzyl chloride is iso-
lated. Chloroformate 1 is formed initially, and if the alcohol is activated, as in the
case of benzyl alcohol, decomposition ensues under these conditions, generating
benzyl chloride in 90% yield [5]. (If the alcohol is not activated, decomposition will
not occur.) Optimizations aimed at achieving higher yields of chloroformate 1 from
the reaction of benzyl alcohol with triphosgene without a base led to a maximum of
15% of 1 besides 2 [4].
2
-R-taxol-7-oxycarbonyl imidazole 4
Comparing the formation of chloroformate 3 with triphosgene and of oxycarbonyl
imidazole 4 with CDI, respectively, as activated intermediates for the preparation of
carbamates at 7-O-taxol shows that, under similar reaction conditions, CDI yields
better results than triphosgene [6] (see Section 4.2.1).
O
-O-R-Taxol-7-chloroformate 3 and 2
O
O
O
Cl
6 eq
(Cl
3
CO)
2
CO
60-70 %
3
O
7
C
O
O
O
9 eq
DIEA
or pyridine
OH
H
O
NH
O
OAc
7
2´
B
O
A
O
C
O
OR
H
O
N
H
O
O
O
3 eq CDI
O
N
7
2´-O-R-
Taxol
C
CH
2
Cl
2
rt, 5 h
94 %
4
O
H
OAc
Reaction of 2
0
-O-R-taxol with triphosgene requires a six-fold excess of the reagent
and at least a nine-fold excess of base providing a 60-70% yield of 3, which is
