Chemistry Reference
In-Depth Information
[666, 667]. A wide variety of N-protected amino acid arylamides 940 are prepared in
this way in good yields.
O
O
O
Boc
2
O
CO
2
+
+
H
pyridine
dioxane
R
O
O
R
OH
937
938
939
H
2
N
NO
2
O
+
CO
2
+
R-CO
2
H = Z-Pro-OH
NO
2
H
O
R
H
940
Typical procedure. Z-Pro-NHNp 940 [666]:
A solution of Z-Pro-OH 937 (2.7 g, 10.7
mmol), pyridine (0.5 mL), and Boc
2
O (2.5 g, 11.4 mmol) in dioxane (10 mL) was
stirred for 0.5 h (50 mL of CO
2
was evolved). Then, a solution of p-nitroaniline 939
(1.5 g, 10.8 mmol) in dioxane (5 mL) was added over a period of 1 h. After stirring
for a further 16 h (a small amount of a yellow solid was formed), the mixture was
diluted with ethyl acetate, filtered, and washed with water, 5% citric acid, 3% am-
monia, water, and brine, dried over MgSO
4
, and the solvent was evaporated. The
residue was crystallized from diethyl ether. Yield 2.6 g (66%) of Z-Pro-NHNp;
R
f
0.78 (toluene/chloroform/acetone/isopropanol, 10:6:5:1).
In a similar manner, Boc
2
O is employed to perform esterifications via highly ac-
tivated acyl carbonates [668].
During the synthesis of eight-membered lactam dipeptides, the primary alcohol
function is protected with an O-Boc residue [669]. The protective group is intro-
duced with Boc
2
O to afford 942 and 943.
ΒΌ
Boc
2
O
(4 equiv.)
+
Boc-O
Boc-O
H
O
DMAP
CH
2
Cl
2
, Et
3
N
rt, 7 d
N
H
H
O
O
O
Boc
941
942
943
71 %
14 %
Typical procedure. (8R)-1-tert-Butyloxycarbonyl-8-tert-butyloxycarbonyloxymethyl-
1,2,3,4,5,8-hexahydroazocin-2-one 942 [669]:
A solution of lactam 941 (157 mg, 1.01
mmol), Boc
2
O (932 mg, 4.14 mmol), DMAP (251 mg, 2.03 mmol), and triethyl-
amine (0.3 mL, 0.138 mmol) in dichloromethane (50 mL) was stirred at room
temperature for 7 d. The reaction mixture was then concentrated in vacuo and
purified by flash chromatography on silica gel eluting with hexane/ethyl acetate
