Chemistry Reference
In-Depth Information
hexane/EtOAc (5:1) afforded 584 (1.29 g, 88% yield) as an oil. Under the same
conditions, the (4R,5R)-isomer of 584 was obtained in 86% yield (1.12 g) from the
(2R,3R) isomer of 583 (1.30 g, 6.28 mmol).
Oxazolidin-2-one 586 formation with benzyl chloroformate in the presence of
excess Et
3
N at room temperature was reported as a key step in the synthesis of
potent HIV-1 protease inhibitors by employing carbohydrate alditols as templates
[411].
PhO
PhO
OH
OH
1. H
2
, Pd-C
N
3
N
3
N
3
HN
O
OH
2.
BnOCOCl
, Et
3
N
OPh
OPh
O
28 %
585
586
Benzyl chloroformate has also been employed as a cyclocarbamation agent in the
presence of aqueous alkali (1 m NaOH, 5
C) for the preparation of the corre-
sponding oxazolidin-2-ones of 3-amino-2-hydroxy-4-methyl-hexadecanoic and 3-amino-
2-hydroxy-4-methyl-14-oxo-octadecanoic acids, respectively [412], (2RS,3SR)-2-amino-
3-hydroxy-3-phenylpropionic acid [413], and
DL
-threonine [414].
(4S,5R)-5-Methyl-2-oxazolidinone-4-carboxylic acid 587 was prepared from l-
threonine with methyl chloroformate [415, 416].
O
MeOCOCl
HN
O
L-Threonine
HOOC
CH
3
587
Typical procedure. (4S,5R)-5-Methyl-2-oxazolidinone-4-carboxylic acid 587 [415]:
To a
solution of l-threonine (2.38 g, 20 mmol) and a trace of thymolphthalein as indi-
cator in 2 n NaOH (30 mL) at 0
C, methyl chloroformate (2.4 mL, 30 mmol) was
added dropwise. To maintain pH 10, it was necessary to add further portions of
NaOH at intervals. The solution was allowed to slowly warm to room temperature
and was stirred overnight. The reaction mixture was then neutralized with dilute
HCl. After evaporation of the volatiles, a white precipitate was obtained. The prod-
uct was extracted with ethyl acetate (250 mL), which was acidified with HCl. The
solvent was again evaporated and the white product was recrystallized from ethyl
acetate/petroleum ether (40/60) to afford 2.18 g (75%) of oxazolidinone 587.
Ureas incorporating structurally complex frameworks, including amino acid de-
rivatives, are e
ciently prepared from 4-nitrophenylchloroformate 589. To give an
example, S-methyl-O-benzyl-l-penicillamine 588 reacts with 589 in acetonitrile at
