17β-tert-Butoxy-gα-androst-2-ene could be produced through the following synthetic routes.

A. Protection of the 17-hydroxyl group. A solution of androstanolone (4.10 g, 14 mmol) in 60 mL of dichloromethane in a 250-mL, one-necked, round-bottomed flask equipped with a magnetic stirring bar and a rubber septum bearing two syringe needles ( inlet and exit) is cooled to -20°C (refrigerated bath). Argon is allowed to pass over the surface of the mixture for 15 min and then boron trifluoride etherate, 0.125 mL, 0.90 mmol) is added rapidly, via syringe, followed by anhydrous phosphoric acid (0.053 mL, 1.0 mmol). Isobutene is added as a gas through a large-bore syringe needle until approximately 100 mL has condensed. The steroid precipitates during addition of the isobutene and redissolves as the reaction proceeds. The drying tube is replaced with a stopper, the tightly sealed flask is allowed to warm to 25°C, and the mixture is stirred at this temperature for 4 hr. The flask is cooled to 0°C, opened, and warmed to 25°C to allow excess isobutene to evaporate. The residue is poured into 2 N aqueous ammonium hydroxide (100 mL) and ethyl acetate (75 mL) is added. After the layers are vigorously shaken, the aqueous solution is washed with a second portion of ethyl acetate. The combined organic extracts are washed with saturated chloride solution, dried over anhydrous magnesium sulfate, filtered, and concentrated by rotary evaporation. The residue is recrystallized from hexane to give colorless crystals, mp 146–148°C, 4.10 g (86%).

B. Preparation and reductive cleavage of the vinyl phosphorodiamidate. A dry, 250-mL flask equipped with magnetic stirrer, syringe port, and argon outlet is flushed three times with argon. To the flask are added 40 mL of dry tetrahydrofuran (THF) and 1.17 mL (8.4 mmol) of dry diisopropylamine. The flask is cooled in an acetone–dry-ice bath while 7.4 mmol of butyllithium in hexane is added dropwise with stirring. After the addition is complete, the solution is allowed to warm for 15 min. The flask is then cooled in an ice–water bath. To this solution is added 1.61 g (4.6 mmol) of 17β-tert-butoxy-5α-androstan-3-one in 30 mL of 2:1 THF/DMPU solution. The reaction mixture is stirred with ice cooling for 15 min. N,N,N',N'-Tetramethyldiamidophosphorochloridate, 5.83 mL (0.038 mol), is added dropwise with stirring. After 15 min, the bath is removed; the flask is allowed to warm to 25°C and is stirred for an additional 2 hr. The excess reagent is hydrolyzed by slow addition of 30 mL of saturated aqueous sodium bicarbonate solution and stirring for 30 min. After three extractions with 100-mL portions of diethyl ether, the combined organic layers are washed twice with 100 mL of water and 100 mL of saturated sodium chloride solution. The solution is dried over anhydrous magnesium sulfate and the ether is removed under reduced pressure on a rotary evaporator to afford 2.9–3.0 g of a crude yellow solid. The crude phosphorodiamidate is dissolved in 40 mL of dry THF and added to a dry, three-necked, 250-mL flask equipped with overhead stirrer, cold finger condenser (acetone–dry ice), argon bubbler, and acetone–dry-ice bath. Dry ammonia is distilled into the flask until the phosphorodiamidate begins to precipitate. The bath is removed and the solution is allowed to warm to reflux. Dry tert-butyl alcohol (1.75 mL) is added in one portion. To the clear solution is added 1.5 cm of 1/8-in., cleaned lithium wire in 0.3-cm portions. The blue color is maintained (by the addition of lithium wire if necessary) with stirring for 4 hr and then allowing the stirred solution to warm to room temperature overnight. is added in 25-mg portions until the blue color is discharged. (0.50 g) is added in one portion, the condenser removed, and the ammonia allowed to evaporate. The residue is taken up in 100 mL of diethyl ether and 100 mL of water. The layers are separated and the aqueous phase is extracted with 100 mL of diethyl ether. The combined organic layers are washed with 100 mL of saturated aqueous sodium chloride solution, dried over anhydrous magnesium sulfate, and filtered. The ether is removed under reduced pressure on a rotary evaporator. The crude olefin is filtered through 15 g of silica gel using benzene–ethyl acetate (2:1) as eluant, to give an off-white solid that is recrystallized from a minimum amount of absolute ethanol to give, after drying, 1.0 g (67%) of 17β-tert-butoxy-5α-androst-2-ene, mp 114–117°C.