Chemistry Reference
In-Depth Information
965
968
O
O
80 % (3 steps)
O
O
O
O
O
O
O
H
O
BnO
O
NaOMe
reflux, 3 h
DMC
O
H
H
O
O
O
O
O
BnO
O
BnO
O
966
967
Typical procedure. 3-O-Benzyl-1,2-O-isopropylidene-a-
d
-glucofuranose-5,6-carbonate 968
[679]:
A solution of diacetone glucose 965 (52 g, 0.2 mol) in dry THF (480 mL)
was added dropwise, with cooling and stirring, to a suspension of sodium hydride
(50% dispersion in oil, washed with hexane, 10.6 g, 1.1 equiv.) in THF (60 mL).
Benzyl bromide (26 mL, 1.1 equiv.) and tetrabutylammonium iodide (0.6 g) were
added and the mixture was refluxed for 45 min. The solution was then cooled, fil-
tered through Celite, and concentrated to a yellow syrup (79 g), which was used
directly in the next step. The crude 966 (79 g) was dissolved in methanol (400 mL)
containing concentrated hydrochloric acid (2.2 mL) and water (40 mL) and stirred
at room temperature. After 20 h, TLC (diethyl ether/hexane, 2:1) showed that the
starting material (R
f
0.2)
had been formed. The solution was neutralized with aq. ammonia (specific gravity
0.88) and concentrated to a syrup, which was dissolved in ethyl acetate (400 mL)
and washed with water (2
¼
0.9) had been consumed and that one product (R
f
¼
400 mL). Evaporation of the solvent gave a crude syrup
of 3-O-benzyl-1,2-O-isopropylidene-a-d-glucofuranose 967, which was dissolved
in DMC (400 mL) and refluxed for 3 h with sodium methoxide (10 g, 185 mmol).
The reflux condenser was then replaced with a stillhead and heating was
continued until the stillhead thermometer reached 90
C (approximately 2 h).
Further DMC was added at intervals to keep the volume of the reaction mixture
constant. At this stage, TLC showed that the conversion to carbonate 968 was
complete. The solution was cooled, washed with water (500 mL), and concentrated
to a syrup, which crystallized spontaneously upon addition of diethyl ether to af-
ford 3-O-benzyl-1,2-O-isopropylidene-a-d-glucofuranose-5,6-carbonate 968 (54 g, 80%
yield based on 965), as colorless crystals; mp 119-120
C, [a]
20
D
¼
52.2 (c
¼
1.15
in CHCl
3
).
