Chemistry Reference
In-Depth Information
while the reaction mixture warmed to room temperature. The mixture was then
acidified to Congo red by the gradual addition of concentrated hydrochloric acid,
and the oil was extracted into ethyl acetate. The extract was dried over magne-
sium sulfate, the mixture was filtered, and the filtrate was concentrated in vacuo.
The residue was extracted/triturated with warm tetrachloromethane. The washings
were decanted and the residue was further purified by recrystallization from ethyl
acetate/petroleum ether. Product: 18.1 g, 89%, mp 76-77
C; [a]
D
21
¼
61
:
7
3, acetic acid); [a]
21
D
(c
¼
5
:
¼
60
:
6(c
¼
2, ethyl acetate).
O
O
PhCH
2
OH (1 equiv)
PhMe or THF
N
O
N
O
O
Cl
pyridine, 3h, 35 °C
O
O
O
O
520
521
alanine, NEt
3
dioxane-H
2
O
COOH
NHCbz
91 %
522
The tert-butoxycarbonyl group (Boc) is one of the most advantageous protecting
groups in the preparation of complicated peptides. For peptides containing me-
thionine, the Boc group offers some advantages over the carbobenzoxy group
(Z, Cbz) [378]. The principal disadvantage to the use of the Boc group lies in the
di
culty of preparing and storing tert-butyl chloroformate. The instability of tert-
butyl chloroformate precludes its use for preparing Boc derivatives and hence a
large number of a1ternative reagents and methods have been developed.
Although t-butyl azidoformate [373-375], t-butyl p-nitrophenyl carbonate [376],
and t-butyl cyanoformate [375] have been recommended as t-butoxycarbonylating
reagents, these cannot be synthesized as easily as benzyloxycarbonyl chloride.
Amino acid esters 523 are readily converted to isocyanates 524 with phosgene
[377], and these will react with tert-butyl alcohol to form Boc-amino acids 525.
R
R
COCl
2
OEt
OEt
H
2
N
O
C
N
O
O
523
524
Me
Me
O
R
Me
Me
Me
OH
OEt
Me
O
H
O
525
