A
1-L, three-necked, round-bottomed flask fitted with a
thermometer,
addition funnel, and an
air motor-driven paddle stirrer is charged with
35.2 g (0.20 mol) of erythorbic acid (Note
1) and 500 mL of deionized water. The solution is stirred with
ice bath cooling (Note
2), and
42.4 g (0.40 mol) of anhydrous, powdered sodium carbonate (Note
3) is added in small portions (Note
4). The resulting yellow solution (Note
5) is stirred with ice-bath cooling while
44 mL (0.45 mmol) of 31.3% by weight aqueous hydrogen peroxide (Note
6) is added dropwise over a 10-min period. The internal temperature rises from 6 to 19°C (Note
7). The solution, containing a few solid particles, is stirred for 5 min with ice bath cooling, during which time the internal temperature continues to rise to 27°C. The flask is now immersed in a
water bath that is heated to 42°C. The solution is stirred for 30 min, during which time the internal temperature reaches a maximum of 42°C (Note
8).
Norit A (8 g) is added in portions over 10 min to decompose the excess peroxide and the mixture is heated on a
steam bath with continued stirring for 30 min, at which point gas evolution has essentially ceased and a negative starch–iodide test is observed. The internal temperature reaches and is kept at 75–78°C. The hot mixture is filtered with suction on a Celite pad into a
2-L, three-necked, round-bottomed flask and the filtercake is washed, in several small portions, with a total of 100 mL of deionized water. The combined filtrate and washes are acidified to pH 1 by the
cautious (Note
9) addition of
150 mL (0.90 mol) of 6 N aqueous hydrochloric acid, in portions, with swirling. The acidic solution is concentrated with a
rotary evaporator at 50°C/water aspirator pressure. The residue is dried at 50°C/0.2 mm to give
84.6 g of a pale-yellow solid residue containing
D-erythronolactone,
oxalic acid, and
sodium chloride (Note
10) and (Note
11). To this material is added
175 mL of acetone (Note
13) and the mixture is swirled to loosen the solids caked on the sides of the flask. A
50-g portion of anhydrous, powdered magnesium sulfate (Note
14) is now added and the mixture is stirred by means of an
air motor-driven paddle stirrer as
350 mL (2.85 mol) of 2,2-dimethoxypropane (Note
15) is added in one portion. To the stirred mixture is added
0.42 g (0.0022 mol) of p-toluenesulfonic acid monohydrate at room temperature. The slurry is blanketed with
nitrogen and stirred at room temperature for 18 hr. In a
2-L, three-necked, round-bottomed flask fitted with a thermometer and an air motor-driven paddle stirrer, a mixture of
500 mL of anhydrous ether and
61.3 mL (0.44 mol) of triethylamine (Note
16) is cooled in an ice bath to 5°C. The reaction mixture is decanted into this solution. The residual solids are rinsed with
60 mL of ether, which is also decanted into the
triethylamine solution. After being stirred for a few minutes (Note
17), the mixture is filtered with suction on a
600-mL, coarse, sintered-glass funnel. The solids are washed thoroughly with a total of
300 mL of anhydrous ether by slurrying three times on the funnel with the vacuum turned off; the vacuum is then applied to draw the wash
ether through the funnel. The filtrate and washes are combined and concentrated with a rotary evaporator at water aspirator pressure, and the residue is dried at 45°C/0.5 mm to give
34.3 g of a pale-yellow solid (Note
18). This material is dissolved in approximately
150 mL of 1 : 1 hexanes : ethyl acetate and the solution (Note
19) is adsorbed on a
column of 200 g of silica gel (Note
20) packed in 1 : 1
hexanes :
ethyl acetate. The column is eluted with a total volume of
2 L of 1 : 1 hexanes : ethyl acetate (Note
21). The eluate is concentrated with a rotary evaporator at aspirator pressure and the solid residue is dried under high vacuum to afford
27.3 g of a colorless solid. This material, contained in a
1-L, one-necked, round-bottomed flask, is treated with
150 mL of anhydrous ether and the mixture is refluxed on a steam bath for 5 min to dissolve all the solid. The solution is removed from the steam bath and treated with
225 mL of hexanes. An immediate precipitate results. The mixture is refrigerated (0°C) for 3.5 hr and then filtered with suction. The solid is washed with a total of
100 mL of hexanes, in small portions, and then dried under high vacuum at 20°C. There is obtained
23.6 g (
74.7%) of
2,3-O-isopropylidene-D-erythronolactone as a white solid, mp
65.5–66°C,
[α]25D −113.8° (
c 1.11
H2O) (Note
22),(Note
23),(Note
24),(Note
25).