To a solution of
0.200 g. (0.515 mmole) of dry dihydrocholesterol (Note
1) in
10 ml. of methylene chloride contained in a
50-ml. Erlenmeyer flask is added
0.3 ml. of a catalyst stock solution containing 0.0016 ml. (0.018 mmole) of concentrated fluoboric acid (Note
2) in
3:1 anhydrous diethyl ether-methylene chloride (Note
3). The solution is swirled, and a
0.45M solution of diazomethane (Note
4) in dry
methylene chloride is added from a
buret (Note
5) at a rate of about 2 ml. per minute. The yellow color of
diazomethane disappears rapidly on contact with the reaction mixture and
nitrogen is vigorously evolved. When about
3 ml. of diazomethane solution has been added, the reaction becomes sluggish. The yellow color persists for several minutes after the total amount of
3.9 ml. of diazomethane solution (1.76 mmoles) has been added (Note
6). After 1 hour the reaction mixture is filtered to remove a small amount of amorphous
polymethylene, which is washed with
methylene chloride. The washings are combined with the
methylene chloride solution, washed with
5 ml. of saturated aqueous sodium bicarbonate, with three 5-ml. portions of water, and dried over anhydrous
sodium sulfate. The solvent is removed on a
steam bath in a stream of
nitrogen and finally at reduced pressure. The crystalline residue of
0.207 g. (Note
7) is recrystallized in a
10-ml. conical flask from
1 ml. of acetone. When the flask has cooled to room temperature,
0.5 ml. of methanol is added, and the flask is chilled to +2° for 2 hours. The crystals are collected on a tared
Hirsch funnel of 40-mm. diameter, washed on the funnel with two
0.5-ml. portions of ice-cold methanol, and dried for 2 hours at 40°/2 mm. The first crop of
cholestanyl methyl ether thus obtained forms large colorless glistening plates, m.p.
85.5–86° (Note
8). An additional
0.002 g. of pure methyl ether adheres to the flask and
spatula and is collected by washing with
acetone. The total first crop material (
0.197 g.) represents a
95% yield of methyl ether (Note
9).