Chemistry Reference
In-Depth Information
Typical procedure. N-Cyclopropyl-6,7-difluoro-2H-1,3-benzoxazine-2,4(1H)-dione 1239
[915]:
In a 10 mL single-necked, round-bottomed flask equipped with a sep-
tum and magnetic stirring bar was placed a solution of 2-N-cyclopropylamino-4,5-
difluorobenzoic acid 1238 (100 mg, 0.46 mmol), and triethylamine (62
L, 0.44
mmol) in dichloromethane (2 mL). The solution was cooled to 0
C, and then
treated with a solution of triphosgene (45 mg, 0.147 mmol) in dichloromethane
(0.5 mL). Finally, a catalytic amount of dimethylaminopyridine (10 mg) was in-
troduced as a solution in dichloromethane (0.5 mL). After stirring at 0
C for 1.5 h,
the reaction mixture was quenched by adding a small amount of 1 n hydrochloric
acid. The organic phase was dried over sodium sulfate and then concentrated to a
yellow oil to afford 114 mg of N-cyclopropyl-6,7-difluoro-2H-1,3-benzoxazine-
2,4(1H)-dione 1239 in quantitative yield. The product was crystallized from hot
ethanol.
Various substituted isatoic anhydrides 1241 have been prepared from the corre-
sponding anthranilic acid 1240 and triphosgene in dioxane (better solvent) or THF
at reflux temperatures; see Table 4.42 [916, 917].
m
R
1
R
1
R'
R
2
R
2
NHR'
N
O
(CCl
3
O)
2
CO
O
Dioxane or
THF
R
3
R
3
COOH
R
4
R
4
O
1240
1241
Typical procedure. Isatoic anhydride 1241 [916]:
Anthranilic acid (5 g, 0.036 mol)
and triphosgene (7.1 g, 0.024 mol) were dissolved in dioxane (75 mL) and the so-
Tab. 4.42.
Preparation of isatoic anhydrides with triphosgene.
Entry
R
1
R
2
R
3
R
4
R
O
Solvent
Time (h)
Yield (%)
1
H
H
H
H
H
Dioxane
14
83.5
H
H
H
H
H
THF
39
70.7
2
H
H
NO
2
H
H
Dioxane
17
91.3
H
H
NO
2
H
H
THF
72
70.0
3
H
H
H
F
H
THF
50
93.5
4
H
H
H
Cl
H
THF
73
99.2
5
H
H
Br
H
H
THF
92
93.8
6
Br
H
Br
H
H
Dioxane
15
88.2
Br
H
Br
H
H
THF
68
65.6
7
Br
H
Br
F
H
THF
36
75.4
8
Br HC
3
H
H
THF
71
77.0
9
H
OCH
3
OCH
3
H
H
Dioxane
19
87.2
10
H
OCH
3
OCH
3
H
H
THF
56
97.0
11
OCH
3
OCH
3
OCH
3
H
H
THF
54
98.5
12
H
H
H
CH
3
H
THF
53
43.5
H
H
H
H
CH
3
Dioxane
18
78.5
