Chemistry Reference
In-Depth Information
Cl
3
COCOCl
1. TiCl
4
2.
CHO
NMM
CO
2
Me
CH
2
Cl
20 h
CO
2
Me
OH
Cl
-30°C, 2 h
Cl
Cl
N
NH
Ti
O
H
CO
2
Me
CO
2
Me
C
H
O
NHCHO
NC
1536
79 %
1534
1533
1535
Typical procedure. Methyl (S)-2-isocyano-3-phenylpropionate 1534 [1172]:
In a 250-mL
three-necked flask equipped with a dry-ice reflux condenser, a dropping funnel,
and a rubber septum, N-formyl-(R)-phenylalanine methyl ester (10.0 g, 48.3 mmol)
{[a]
D
0 in ethanol)} was dissolved in dichloromethane (60 mL)
under an argon atmosphere. The solution was initially cooled to
¼
31
:
7(c
¼
1
:
10
C and N-
methylmorpholine (10.4 mL, 94 mmol) was added by means of a syringe; then, at a
temperature of
30
C, a solution of diphosgene (2.9 mL, 24 mmol) in dichloro-
methane (10 mL) was added from the dropping funnel at such a rate that the in-
ternal temperature did not exceed
30
C. The orange suspension was stirred for 2
h at this temperature and then allowed to warm slowly to
15
C. The mixture was
then hydrolyzed with ice/water (40 mL) and the aqueous layer was extracted with
dichloromethane (3
40 mL). The combined organic layers were washed twice
with 7.5% aq. NaHCO
3
solution and once with water, and dried over 4
˚
molecular
sieves at
30
C for 10 h. The crude product was purified by flash chromatography
on silica gel, eluting with pentane/ethyl acetate (7:3). The product 1534 was ob-
tained as red-orange crystals: 7.2 g (79%), mp 57-58
C, [a]
D
¼
13
:
2(c
¼
1
:
3in
benzene).
Methyl (R)-2-isocyano-3-phenylpropionate was prepared in the same way as
above: yield 4.8 g (53%); mp 58-59
C, [a]
D
0 in methanol).
3,3,3-Trifluoro-2-isocyano propionates, versatile building blocks for the intro-
duction of trifluoromethyl groups into organic molecules, are synthesized using
diphosgene to dehydrate the corresponding formamides to give the desired iso-
cyanides in yields of 60-88% [1173].
¼þ
18
:
6(c
¼
1
:
O
O
1537
NC
O
O
O
A crown ether containing an isocyanide group, 1537,ap-acceptor macrocycle, has
been prepared by dehydration of the corresponding formamide with diphosgene,
