To a 5-l. three-necked flask, equipped with a sealed mechanical stirrer, a dropping funnel, and a take-off reflux condenser, are added 2 l. of sulfur-free toluene and two boiling chips. The openings of the dropping funnel and the condenser are protected by drying tubes containing Drierite. A portion (200 ml.) of the toluene is distilled from the flask (take-off cock open) in order to dry the system by azeotropic distillation; then 100 g. (0.26 mole) of cholesterol and 500 ml. of cyclohexanone (Note 1) are added to the flask. After an additional 50 ml. of toluene has been distilled, a solution of 28 g. (0.14 mole) of aluminum isopropoxide (Note 2) in 400 ml. of dry toluene (Note 3) is added dropwise over a period of approximately 30 minutes. During this time toluene is distilled at a rate slightly greater than the rate of addition of catalyst solution, so that when the addition is complete about 600 ml. of toluene has distilled. An additional 300 ml. of toluene is distilled, and the murky orange-colored reaction mixture is then allowed to cool to room temperature.

Four hundred milliliters of a saturated aqueous solution of potassium-sodium tartrate (Note 4) is added to the mixture, and the organic layer becomes clear and orange. The stirrer assembly is removed, and the mixture is steam-distilled until about 6 l. of distillate has been collected. The residual mixture is cooled and extracted successively with one 300-ml. portion and two 100-ml. portions of chloroform. The combined extracts are washed with two 100-ml. portions of water and dried over anhydrous magnesium sulfate. The chloroform is removed by distillation on the steam bath at reduced pressure (water aspirator). The residual viscous amber oil (Note 5) is dissolved by heating in 150 ml. of methanol. When the solution has cooled to about 40°, seeds of cholestenone are added, and the flask is wrapped with a small towel to ensure slow cooling (Note 6). After the bulk of the material has crystallized, which requires several hours, the mixture is stored at 0° overnight (Note 7). The product is collected by suction filtration, washed with 40–50 ml. of methanol previously cooled in an ice-salt bath, then dried at reduced pressure, first at room temperature and finally at 60°. The yield of light-cream-colored Δ⁴-cholesten-3-one is 81–93 g. (81–93%), m.p. 76–79°. Recrystallization from methanol gives material melting at 79.5–80.5° in 90% recovery (Note 8).