Chemistry Reference
In-Depth Information
545], potassium cyanate (only 5% yield) [546], CDI [547], the use of which results
in the formation of an undesired by-product [548], and triphosgene [549].
The employment of triphosgene has the particular advantage that it can be
directly applied to deoxygenated THF solutions of 2-amino-5-methoxyphenol 751
derived from the reduction of the corresponding nitro derivative 750 [549].
Typical procedure. 6-Methoxy-2-oxo-2,3-dihydrobenzoxazole (MBOA) [549]:
A solution
of 5-methoxy-2-nitrophenol 750 (3.38 g, 20 mmol) in absolute THF (80 mL) con-
taining 10% Pd/C catalyst (100 mg) was hydrogenated at ambient temperature and
pressure until the calculated amount of H
2
(1344 cm
3
) had been taken up. The
resultant colorless solution was treated, with stirring and external cooling under N
2
atmosphere, with triethylamine (4.04 g, 40 mmol) in a single portion, followed
rapidly by a solution of triphosgene (2.0 g, 6.7 mmol) in THF (20 mL). After 30
min, Et
3
N
HCl and the catalyst were removed by suction, and THF was completely
removed from the filtrate under reduced pressure. The pale-brown crystalline resi-
due was redissolved in boiling benzene (200 mL) and the solution was filtered
while hot through a filter pad of 4 cm silica gel (0.063-0.200 mm). The filter pad
was then washed with hot benzene (150 mL). Cooling of the filtrate afforded the
product 6-methoxy-2-oxo-2,3-dihydrobenzoxazole 752 as colorless needles, which
were isolated by suction filtration; yield 2.5 g (75%).
An interesting transformation of the b-lactam acetonide 753 into the oxazo-
lidinone 754 has been accomplished by simple hydrolysis followed by recyclization
with triphosgene [550].
O
O
N
N
O
O
1. 0.2N HCl, THF, 25°C
2.
(CCl
3
O)
2
CO
,
i-Pr
2
NEt, CH
2
Cl
2
, 0°C
O
N
N
O
O
91 %
753
754
Typical procedure. (6R,7R)/(6S,7S)-7-[(4R/4S)-2-Oxo-4-phenyl-1,3-oxazolidin-3-yl]-1-aza-
5-oxabicyclo[4.2.0]octan-8-one 754 [550]:
A solution of b-lactam acetonide 753 (2.30 g,
7.6 mmol) in THF/0.2 n HCl (1:1; 120 mL) was stirred at 25
C for 45 min. After
removal of the THF under reduced pressure, the mixture was neutralized with
saturated aq. NaHCO
3
solution, extracted with dichloromethane (4
100 mL), and
the combined extracts were dried over MgSO
4
, filtered, and concentrated to afford
2.07 g of crude product containing the free amino alcohol. The crude product was
redissolved in dichloromethane (150 mL) and this solution was cooled to 0
C.
Diisopropylethylamine (3.71 g, 28.7 mmol) was added and, after 5 min at 0
C,
triphosgene (1.9 g, 6.4 mmol) was added portionwise with a spatula. After stirring
for 45 min at 0
C, the mixture was filtered through a short pad of silica gel and
the filtrate was concentrated. Chromatography (SiO
2
, 150 g; eluent CH
2
Cl
2
/EtOAc,
3:1) afforded (6R,7R)/(6S,7S)-7-[(4R/4S)-2-oxo-4-phenyl-1,3-oxazolidin-3-yl]-1-aza-
5-oxabicyclo[4.2.0]octan-8-one 754 (2.0 g, 91%).
