Chemistry Reference
In-Depth Information
5-Chloro-2,3-dihydro-2,2-dimethylbenzofuran-7-carboxylic acid 1347 was acti-
vated for esterification by reaction with either triphosgene/Et
3
N/DMAP or diphos-
gene/Et
3
N [1020].
Me
Me
O
Me
O
Me
O
O
(CCl
3
O)
2
CO
Et
3
N-DMAP
Cl
OH
Cl
Cl
1348
1347
Thiazolecarbonyl chloride was prepared in 88% yield by adding triphosgene to a
suspension of the corresponding acid in toluene and refluxing the mixture for 15 h
[1021].
CH
3
CH
3
N
N
(CCl
3
O)
2
CO
H
3
C
H
3
C
Toluene, reflux
S
S
COOH
COCl
1349
1350
The use of triphosgene as an acid activator has been reported in several recent ap-
plications. Eckert and Seidel activated the N-protected amino acid Tcboc-valine
1351 (Tcboc
2,2,2-trichloro-tert-butyloxycarbonyl [1022]; for a preparation, see
also Section 4.3.2.1) with triphosgene/DMF/TEA for racemization-free coupling
with valine benzyl ester to afford Tcboc
¼
a
Val
a
Val
a
OBn in 85% yield [1023, 1024].
TEAH
+
Cl
DMF
CO
2
TEA
DMF
1/3
(CCl
3
O)
2
CO
H-Val-OBn
1353
TEA
TEAH
+
Cl
*
Tcboc-Val-Val-OBn
Tcboc-Val-OH
Tcboc-Val-Cl
1351
1352
1354
Tcboc = 2,2,2-trichloro-tert-butyloxycarbonyl
The method is particularly well-suited for coupling N-alkyl amino acids. Tcboc
a
Phe
ferrocenylmethyl [1025, 1026])
can be coupled with triphosgene/DMF/TEA to afford moderate to excellent yields
(50-97%) of Tcboc
a
OH 1355 and FemLeu
a
OtBu 1357 (Fem
¼
OtBu 1358, depending on the excess of the acti-
vated component 1356 [1023, 1024].
An original process has been reported in which triphosgene is used as an e
-
cient and effective coupling reagent for peptide synthesis through in situ genera-
a
Phe
a
FemLeu
a
