Chemistry Reference
In-Depth Information
CH
3
O
l
H
3
C
Cl
H
3
C
OO
Cl
Cl
Cl
CH
3
O
R
R
774
H
3
C
Cl
O
+
Cl
H
3
C
O
H
COOH
H
2
N
H
Dioxane, H
2
O, Et
3
N, 20 °C
H
78-91 %
773
775
776
Di-tert-butyl dicarbonate (Boc
2
O)
Protection of amidic nitrogen with di-tert-butyl dicarbonate (Boc
2
O), in acetonitrile
at room temperature, as part of an e
cient and regioselective method for the N-
debenzoylation of Paclitaxel (Taxol
2
) 777 to 10-acetyldocetaxel and to Docetaxel
778, has been reported [566]. Paclitaxel
2
, and its semisynthetic analogue Doce-
taxel (Taxotere
2
), are among the most important new antitumor agents of last
decade.
R
2
O
O
OH
O
R
1
NH
O
O
AcO
Ph
O
OHO
OH
COPH
Paclitaxel
R
1
= Ph, R
2
= Ac,
777
Docetaxel
R
1
=
t
BuO, R
2
= H,
778
O
AcO
OSiEt
3
O
AcO
OSiEt
3
O
t
Bu
O
O
CO
Boc
2
O
, DMAP
Ph
N
O
Ph
NH
O
O
AcO
Ph
O
O
MeCN, rt, 24 h
AcO
Ph
O
OO
OHO
O
O
O
O
Bn
COPh
Bn
O
t
Bu
Ph
O
O
61 %
779
780
Deprotection and further selective N-debenzoylation is accomplished by treatment
with magnesium methoxide in methanol [566].
The preparation of tert-butyl carbamates 782 with Boc
2
O, and their one-pot con-
version to amides 783 with an acyl halide/methanol mixture, has recently been re-
ported [567].
