Chemistry Reference
In-Depth Information
(56 mg, 0.55 mmol) followed by triphosgene (33 mg, 0.22 mmol). The mixture was
stirred for 1 h at 20-25
C and then filtered through silica gel. Removal of the
solvent from the filtrate in vacuo afforded 60 mg (64%) of colorless crystals; mp
65-66
C.
O
O
t-Bu
(CCl
3
O)
2
CO
t-Bu
H
OH
O
H
Base
Cl
NH
2
R
N
R
O
1218
1219
The N-carboxyanhydride of oxaproline is best prepared by treating oxaproline
hydrochloride with di- or triphosgene, followed by N-methyl morpholine cycliza-
tion as illustrated below. The product, which is obtained as white crystals, shows
no sign of racemization by chiral GC [898].
1.
CCl
3
OCOCl
or
(CCl
3
O)
2
CO
, THF, 60°C
O
O
O
N
COOH
* HCl
H
2. N-methyl morpholine, 20 °C
O
O
70 %
1220
1221
The NCA of formyltryptophan has been prepared with triphosgene in 85% yield
[899]. Similarly, NCAs of 4-nitro-g-benzyl-l-glutamate and g-4-trifluoromethyl-
benzyl-l-glutamate have been prepared in yields of 84% and 75%, respectively,
with triphosgene in dioxane [900].
Typical procedure. g-4-Nitrobenzyl-
l
-glutamate N-carboxyanhydride [900]:
A suspen-
sion of g-4-nitrobenzyl-l-glutamate (0.5 g, 1.77 mmol) in dioxane (20 mL) was
stirred for 10 min. Nitrogen was then passed into the suspension for 15 min. The
suspension was slowly heated to 50
C and triphosgene (0.53 g, 1.785 mmol) was
added in a single portion. Elevation of the temperature to 50
C should proceed
slowly. After 2 h, the mixture became almost homogeneous. The solution was kept
at 40
C and nitrogen was passed through it for 2 h in order to remove any residual
phosgene. It was then filtered, and the filtrate was concentrated to leave an oily
residue. A small amount of ethyl acetate was added, with stirring, to dissolve the
oil. When the solution became homogeneous, n-hexane was added dropwise until
the cloud point, and the purged solution was stored at 5
C overnight. Repetition
of the precipitation step yielded g-4-nitrobenzyl-l-glutamate N-carboxyanhydride,
0.46 g, 84% yield.
An unconventional and very interesting method for the synthesis and purifica-
tion of N-carboxyanhydride derivatives of g-alkyl-l-glutamates has recently been
