Chemistry Reference
In-Depth Information
Tab. 4.40.
Yields of the NCA product after application of the
purification method [901].
O
O
O
O
n
H
N
O
1222
n
Scale
a
(g)
Typical yield
(%)
Benzyl
10
69
1
2
67
3
2
86
5
2
71
7
5
69
9
5
44
11
2
61
13
2
45
15
2
36
17
2
49
a
amount of starting amino acid used
published [901]. The hydrochloride salt of the starting amino acid, and triphosgene
itself, which are the main undesired impurities that severely limit the polymeriza-
tion of the NCA, can be effectively removed by washing the reaction mixture with
water and aqueous sodium hydrogen carbonate solution at 0
C prior to isolation
of the NCA, despite the well-known sensitivity of the NCA to water. The method is
particularly useful for NCA derivatives that are isolated as oils, since purifying
them by recrystallization or solvent washes is not feasible. Table 4.40 shows the
yields of the NCA product after application of this purification method.
Typical procedure. NCA of g-benzyl-
l
-glutamate [901]:
g-Benzyl-l-glutamate (10 g,
0.042 mol) was suspended in anhydrous EtOAc (300 mL) in a reaction flask fitted
with a reflux condenser and nitrogen bubbler. After heating to reflux, triphosgene
(4.2 g, 0.014 mol) was added in a single portion and the mixture was kept under
reflux under nitrogen for 4-5 h. Generally, the reaction mixture became clear. In
cases where it did not, a small quantity of triphosgene was added. For oily NCAs,
no additional triphosgene was used. The reaction mixture was allowed to cool to
room temperature, which in some cases led to the precipitation of a solid (pre-
sumably the HCl salt of the starting amino acid). The mixture was then cooled to
5
C in the stoppered reaction vessel.
Isolation and purification procedure: (Note: Work attentively and quickly during
this procedure.) The cold reaction mixture was transferred to a separatory funnel
and washed with deionized water (100 mL) that had been chilled to 0
C. As ex-
