Chemistry Reference
In-Depth Information
Typical procedure for the preparation of NCAs [887]:
l-Leucine (26.2 g, 0.2 mol) and
activated charcoal (0.5 g) were suspended in THF (250 mL). Diphosgene (18 mL,
0.15 mol) was then added to the suspension with vigorous stirring. The tempera-
ture was gradually increased to 55
C, and stirring was continued at this tempera-
ture until the amino acid had dissolved. The solution was then filtered through
Celite placed on a glass filter. The filtrate was concentrated at 40
C under reduced
pressure to give a pale-yellow oil, which was crystallized by the addition of hexane.
The product was twice recrystallized from diethyl ether/hexane to give colorless
crystals of the NCA. Yield 89%.
The NCA of d-4-hydroxyphenylglycine was obtained in 95% yield from the cor-
responding amino acid and diphosgene in THF at 50
C [889].
d/l-Valine 1204 gave the corresponding NCA 1205 in 93% yield when treated
with diphosgene and charcoal in THF at 60
C [890].
O
O
CCl
3
OCOCl
Charcoal
O
OH
THF, 60 °C
N
H
H
2
N
O
1204
1205
Typical procedure for the synthesis of l-valine N-carboxyanhydride, (2S)-4-isopropyl-
oxazolidine-2,5-dione 1205 [887, 890]:
l-Valine (12.9 g, 0.11 mol) and activated
charcoal (0.5 g) were suspended in anhydrous THF (100 mL), and to the suspen-
sion was added diphosgene (10.0 mL, 0.083 mol). The temperature was gradually
increased to 60
C, and the mixture was maintained at this temperature for 1 h.
Excess phosgene was then removed by purging with nitrogen and the suspen-
sion was filtered through Celite. The yellow filtrate was concentrated in vacuo
(
40
C). Addition of pentane (ca. 500 mL) gave crystals of l-valine NCA, which
were recrystallized twice from diethyl ether/pentane (14.32 g, 91%).
4-d-Arabino-tetramethoxybutyl-1,3-oxazolidine-2,5-dione was obtained in 95%
yield by treating 2-amino-2-deoxy-3,4,5,6-tetra-O-methyl-d-gluconic acid hydro-
chloride with diphosgene and active charcoal in THF at 55
C [891].
Similarly, dl-erythro- and threo-4-fluoroglutamic acid have been transformed into
the corresponding NCA 1207 by treatment with diphosgene and active charcoal in
THF at 55
C [892].
<
Triphosgene
O
O
O
O
HH
CCl
3
OCOCl
OH
O
HO
OH
N
H
F
THF, 55 °C
H
2
N
F
O
erythro
1206
1207
