Chemistry Reference
In-Depth Information
COOH
COOH
(CCl
3
O)
2
CO
Y
Y
NH
NH
2
X
1N NaOH, Dioxane
XH
O
736
737
Y = H, Me
X = O, S
a
Y = H, X = O
b
Y = Me, X = O
c
Y = H, X = S
General procedure. 4-Carboxyoxazolidin-2-ones and 4-carboxythiazolidin-2-one 737
[511]:
To a 1 n solution of NaOH (15 mL, 15 mmol) was added l-serine, l-threo-
nine, or l-cysteine (5 mmol), followed by a solution of triphosgene (1.5 g, 5 mmol)
in dioxane (10 mL). The reaction mixture was stirred at room temperature until a
clear solution was obtained and then stirred for a further 1-2 h. The solvent was
then evaporated and the solid residue was extracted with hot acetonitrile (10-15
mL). The extract was filtered, and the filtrate was concentrated to leave an amor-
phous solid, which was crystallized from acetone or acetone/diethyl ether as a cy-
clohexylamine salt (starting from l-threonine, a yield of 72% was reported).
L
-2-Oxothiazolidine-4-carboxylate is a non-toxic precursor of cysteine proposed as
a prodrug capable of penetrating into living cells. Therefore, its oral or parenteral
administering to humans provides a method of restoring the glutathione level of
numerous tissues in which 5-oxoprolinase is present, especially in the liver [520].
In HIV-seropositive patients, it was shown to increase the levels of glutathione, the
lack of which is suspected to be a factor in their immunodeficiency [521].
The reaction of vicinal amino alcohols with triphosgene, in dichloromethane or
tetrahydrofuran in the presence of triethylamine or Hunig's base at ambient tem-
perature, has been reported elsewere [522-528].
A mild procedure for the synthesis of (4R,5S)-4,5-diphenyl-2-oxazolidinone 739
has been described [529]. Compound 739 has been used for the synthesis of opti-
cally active amines [530] because of its high stereoselectivity and easy deprotection
by hydrogenolysis after the reaction. The procedure can also be used to prepare 2-
oxazolidinones from various 2-amino-ethanol derivatives.
Ph
HO
Ph
(CCl
3
O)
2
CO
O
O
CH
2
Cl
2
, T<10 °C
N
H
Ph
H
2
N
Ph
738
739
Typical procedure. (4R,5S)-4,5-Diphenyl-2-oxazolidinone 739 [529]: A 1-L three-
necked, round-bottomed flask, equipped with a magnetic stirrer, a thermometer, a
reflux condenser, and a dropping funnel, was charged with (1S,2R)-(
)-2-amino-
1,2-diphenylethanol (20.0 g, 94 mmol) and dichloromethane (140 mL), and cooled
in an ice/water bath. After the addition of triethylamine (28.4 mL, 204 mmol), a
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