Chemistry Reference
In-Depth Information
anol and dodec-8c-en-1-ol (obtained in 60% yield and possessing significant inhibi-
tory activity) were prepared with triphosgene in THF/pyridine [29].
Typical procedure. (Z)-8-Dodecen-1-yl chloroformate 34 [29]:
A solution of triphos-
gene (0.367 mmol) in dry THF (1 mL) was cooled in an ice-bath and pyridine
(45
L, 1.2 equiv.) was added. To the preformed white precipitate, a solution of the
(Z)-8-dodecen-1-ol (85 mg, 0.466 mmol) in THF (2 mL) was added dropwise
over a period of 20 min. After stirring for 2 h at ice-bath temperature, the reac-
tion mixture was poured onto ice and aq. HCl (3.7%, 0.4 mL). Subsequent stan-
dard work-up and PMPLC afforded the (Z)-8-dodecen-1-yl chloroformate (69 mg,
60% yield).
Activation of the hydroxyl group in vitamin E, 35, to obtain vitamin E modified
monomeric conjugates of 3
0
-deoxyadenosine (cordycepin), which inhibits HIV-1-
induced syncytia formation, has been realized with diphosgene [30].
m
ClOCO
HO
CCl
3
OCOCl
Et
3
N, THF, 0°C
O
O
97 %
35
36
Typical procedure. 2-Ambo-a-tocopheryl chloroformate 36 [30]:
2-Ambo-a-tocopheryl
chloroformate was synthesized by adding dropwise a solution of 2-ambo-a-
tocopherol (431 mg, 1 mmol) and triethylamine (0.14 mL, 1 mmol) in anhydrous
THF to an ice-cooled solution of diphosgene (0.181 mL, 1.5 mmol) in anhydrous
THF (4 mL). After stirring for 30 min at 0
C, a small amount of charcoal was
added, and the mixture was kept for a further 15 min. After two filtrations, the fil-
trate was concentrated to a yellow oil (480 mg, 97%).
The preparation of ethanedithiol mono(b-cyanoethyl carbonate) 40 with isolation
of the intermediate chloroformate 38 has been described [31].
SH
HS
O
O
N
N
(CCl
3
O)
2
CO
39
N
HS
S
O
HO
Cl
O
Pyridine, 0°C
37
38
40
Typical procedure. Ethanedithiol mono(b-cyanoethyl carbonate) 40 [31]: Triphosgene
(24.5 g, 83 mmol) was dissolved in anhydrous toluene (150 mL) and the solution
was cooled to 0
C. Dropwise addition of b-cyanoethanol (17.6 g, 248 mmol) was
followed by dropwise addition of pyridine at 0
C. The reaction mixture was then
filtered to remove pyridine hydrochloride salt and concentrated to an oil. The crude
