Chemistry Reference
In-Depth Information
ture of methyl anthranilate and triethylamine, furnished the target benzyloxyurea
in 72% yield [106]. These conditions circumvent the complications seen by McKay;
the authors reported no evidence of chlorination or isocyanuric acid formation.
H
N
l
NH
2
(CCl
3
O)
2
CO
O
O
O
dioxane, Et
3
N,
100°C
158
163
COOCH
3
NH
2
COOCH
3
N
N
164
O
O
165
Typical procedure. N-Benzyloxyureas 165 by addition of anthranilate 164 to benzyloxy-
carbamoyl chloride 163 [106]:
Triphosgene (600 mg, 2.05 mmol) was added to a
solution of O-benzylhydroxylamine (500 mg, 4.1 mmol) in anhydrous 1,4-dioxane
(25 mL) and, under nitrogen, the reaction flask was immersed in an oil bath heated
to 100
C. After 45 min, the hot solution was cannulated dropwise into a mixture
of the anthranilate (3.15 mmol) and Et
3
N (12 mL, 12 mmol) at 100
C. After cool-
ing to 24
C, the precipitate was filtered off (Et
3
N
HCl), and the filtrate was con-
centrated. The residual oil was diluted with Et
2
O (10 mL), and 1 n anhydrous HCl
in Et
2
O (10 mL) was added. The resulting HCl salt of unconsumed anthranilate
was filtered off, and the filtrate was diluted with EtOAc (50 mL), washed with aq.
NaHCO
3
(20 mL) and brine (20 mL), and dried (Na
2
SO
4
). Concentration in vacuo
and chromatography of the residue gave N-hydroxyureas.
N-Hydroxyureas prepared as described above are valuable intermediates for
the synthesis of N-hydroxypyrimidinediones 168 by cyclization with one equi-
valent of potassium tert-butoxide in benzene at reflux; yields of 85-95% are
obtained (Table 4.5). Alternatively, the latter have been obtained from the N-o-
aminobenzoylhydroxylamine 166 by chlorocarbonylation and further cyclization
[106].
O
O
O
O
OH
N
NHOH
EtOCOCl
N
Cl
OH
dioxane
H
O
NH
2
NH
2
166
167
168
