Chemistry Reference
In-Depth Information
1539
O
OHC-HN
N
N
74 %
O
NC
O
Ph
1543
Ph
Cl
3
COCOCl
-78°C, 15 min
Et
3
N, CH
2
Cl
2
EtOH
O
CN
H
CN
O
O
EtOH
NC
+
NC
O
O
K
2
CO
3
Ph
Ph
1542
rt, 6 h
1540
60 %
1541
Typical procedure. Ethyl 2-cyano-2-isocyano-3-phenylpropanoate 1540 [1178]: To a
stirred solution of 2-cyano-2-formamido-3-phenylpropanoate (0.615 g, 2.5 mmol)
in dichloromethane (7.5 mL) at
78
C, triethylamine (1.75 mL) was added in a
single portion and then diphosgene (0.3 g, 0.183 mL) was added dropwise over a
period of 10 min. The solution turned slightly brown, and a white precipitate was
formed. After stirring for 15 min at
78
C, the mixture was allowed to warm to
room temperature and water (25 mL) was added. The organic layer was sepa-
rated, washed with water, and dried with Na
2
SO
4
. The resulting solution was
filtered through silica (15
1 cm), and the pure product ethyl 2-cyano-2-isocyano-
3-phenylpropanoate 1540 was obtained as a solution in dichloromethane. It could
be stored at
25
C for a few months. Yield: 342 mg (60%); R
f
(hexane/EtOAc,
3:1)
0.49.
The highest functional group density is established in a 1,1,1-trifunctionalized
carbon atom. The same author as above has described syntheses and reactions of
1-cyano-1-isocyanoalkyl-phosphonic acid esters 1544 [1179, 1287].
¼
General procedure. 1-Cyano-1-isocyanoalkylphosphonic acid esters 1544 [1179]:
To a
stirred solution of the 1-cyano-1-(formylamido)alkyl-1-phosphonic acid ester (4.54
mmol) and triethylamine (3.2 mL) in dichloromethane (25 mL) at
78
C, di-
phosgene (0.33 mL, 0.54 g, 2.72 mmol) was added dropwise over a period of 10
min. The mixture was stirred at this temperature for a further 15 min, and then
the cooling bath was removed and water (25 mL, pH 7) was added. The organic
layer was separated, washed with water (30 mL), dried over Na
2
SO
4
, and the sol-
vent was evaporated in vacuo at a temperature below 20
C. Chromatography of the
resulting solution on silica gel (15
2 cm) eluting with diethyl ether/acetone (9:1)
afforded 1-cyano-1-isocyanoalkyl-phosphonic acid esters as colorless to yellow solu-
tions. Yields: 24-98%.
