Chemistry Reference
In-Depth Information
RO
RO
Boc
2
O
RO
OR
RO
OR
DMAP, CH
2
Cl
2
, 30 min, 20 °C
NH
2
NCO
R = H
3
CO
CH
2
80 %
O
474
475
Automated solid-phase synthesis with triphosgene
In investigations on automated solid-phase organic chemistry, transformations in-
volving the use of the highly reactive reagent triphosgene have been conducted
using the ACT Model 496 MOS [324]. In particular, applications to the parallel
synthesis of a variety of urea and urethane derivatives, primarily derived from
amino acid precursors, have been developed.
Since the urea moiety has been reported to be extremely effective in the design
of certain active peptidomimetics, this automated methodology provides an excel-
lent opportunity for further diversity studies in these as well as other systems.
H
R'
N
R
R"
HNR'R"
O
O
O
478
NH
2
resin
NCO
R
R
(CCl
3
O)
2
CO
H
O
O
dipea, rt
O
O
N
O
R
R
resin
resin
ROH
O
O
O
dipea = diisopropylethylamine
resin
476
477
479
4.3.1.6
Acyl Isocyanates
Oxalyl chloride has been used to prepare several acyl isocyanates starting from the
corresponding amides (Table 4.20). All the reactions described below are amide
carbonylations.
O
O
(COCl)
2
R
NH
2
R
NCO
1,2-DCE
480
481
Typical procedure. 4-Toluoyl isocyanate [325]:
Oxalyl chloride (31.7 g, 0.25 mol) in
1,2-dichloroethane was added to 4-toluamide (24.3 g, 0.18 mol) in 1,2-dichloro-
ethane at 0
C. The solution was allowed to warm to room temperature, and then
