Chemistry Reference
In-Depth Information
with hexane/ethyl acetate (10:1) yielded the nitrile 1474 (87.8 mg, 88%); mp 115
C
(from hexane).
According to the p-tosyl chloride method, chiral intermediates bearing cyano
groups 1478 (R
H, Me) are prepared from amino acid starting materials 1476.
The intermediates 1478 can then be transformed to chiral 2-amino-2-(2
0
-pyridyl)-1-
alkanols 1479 [1120] and trans-5-oxohexahydropyrrolo[3,2-b]pyrroles [1121], re-
spectively.
¼
R
1.
2
H
O
R
R
TsCl
O
O
cat.
N
pyridine
80°C
1 h
N
H
2
N
N
CN
2.
4 N HCl
CONH
2
Z
70-88 %
Z
1477
1479
14
H
R
Z
H
CO
2
R´
R = H, Me
1476
General procedure. (4R)-N-Benzyloxycarbonyl-4-cyano-2,2-dimethyl-1,3-oxazolidine and
(4R,5R)-N-Benzyloxycarbonyl-4-cyano-2,2-dimethyl-5-methyl-1,3-oxazolidine 1478 [1120]:
A solution of the amide 1477 (36 mmol), p-tosyl chloride (10.29 g, 54 mmol), and
pyridine (70 mL) was purged with Ar and stirred at 80
C for 1 h. The crude mix-
ture was then concentrated under reduced pressure and diluted with EtOAc (200
mL). The organic phase was washed with 2 n HCl (3
50 mL), water (3
50 mL),
and saturated NaHCO
3
solution (3
50 mL), dried (Na
2
SO
4
), concentrated, and
purified by flash chromatography (dichloromethane/hexane, 1:1); yield 70-88% of
1478.
6,8-Dimethylazulene-4-carbonitrile 1481 has been prepared from the corre-
sponding carbaldoxime 1480 by dehydration with p-tosyl chloride in 77% yield
[1122].
N
OH
NC
TsCl
piperidine
reflux, 8 h
77 %
1480
1481
Typical procedure. 6,8-Dimethylazulene-4-carbonitrile 1481 [1122]:
A mixture of 1480
(996 mg, 5.0 mmol) and p-tosyl chloride (955 mg, 5.0 mmol) in dry piperidine
(50 mL) was heated under reflux for 8 h. After evaporating the piperidine in vacuo,
