(8R,9S,10R,13S,14S)-13-ethyl-1,2,6,7,8,9,10,11,12,14,15,16-dodecahydrocyclopenta[a]phenanthrene-3,17-dione

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Treat dl-13-ethyl-3-methoxygona-2,5(10)-dien-17-one with hydrochloric acid in aqueous methanol to obtain dl-13-ethylgon-4-ene-3,17-dione (25.6, 54% from dl-13-ethyl-3-methoxygona-2,5(10)-dien-17β-ol), m.p. 156°-157.5°; ultraviolet absorption peak in 95% ethanol at 240.5 mμ (15,900), infrared maxima (potassium bromide) at 5.77 μ, 5.98 μ. Recrystallize dl-13-ethylgon-4-ene-3,17-dione (1.0 g) three times from ethyl acetate to obtain 484 mg., 157°-159.5°; ultraviolet absorption peak (95% ethanol) at 240 mμ (ε17,200), infrared maxima (potassium bromide) at 5.77 μ, 5.98 μ.

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Heat 13β-ethyl-3-methoxy-17,17-ethylenedioxy-gona-2,5(10)-diene (0.1 g.) in glacial acetic acid (2.5 cc.) and water (1 cc.) on a steam bath for 20 minutes, bring finally to boiling and allow to cool. Add aqueous sodium bicarbonate to neutralize the solution and ether extract the product. Wash, dry and evaporate the ether extracts to furnish a residue (0.065 g.); crystallize from a mixture of acetone and light petroleum to obtain the title compound (0.01 g.), m.p. 154°-5°; ultraviolet absorption peak at 239 mμ (ε15,000); infrared absorption peaks at 5.75, 5.96 μ. to cool extract the product Wash dry evaporate the ether to furnish a residue (0.065 g.) crystallize from a mixture of acetone and light petroleum

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Heat 13β-ethyl-3-methoxy-17,17-ethylenedioxy-gona-2,5(10)-diene (0.1 g.) in glacial acetic acid (2.5 cc.) and water (1 cc.) on a steam bath for 20 minutes, bring finally to boiling and allow to cool. Add aqueous sodium bicarbonate to neutralize the solution and ether extract the product. Wash, dry and evaporate the ether extracts to furnish a residue (0.065 g.); crystallize from a mixture of acetone and light petroleum to obtain the title compound (0.01 g.), m.p. 154°-5°; ultraviolet absorption peak at 239 mμ (ε15,000); infrared absorption peaks at 5.75, 5.96 μ. to cool extract the product Wash dry evaporate the ether to furnish a residue (0.065 g.) crystallize from a mixture of acetone and light petroleum

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Add 13β-ethyl-gon-5(10)-en-3,17-dione (1 g.) with stirring under nitrogen to methanol (25 cc.) containing 11N hydrochloric acid (1.75 cc.) and water (1.1 cc.). Stir for 2 hours, add sodium bicarbonate (1.75 g.) and filter the mixture. Evaporate the filtrate to dryness and recrystallize the residue from ethyl acetate to obtain the title compound; ultraviolet absorption peak at 240 mμ (ε17,800); infrared absorption peaks at 5.78, 6.00, 6.17 μ. filter the mixture Evaporate the filtrate to dryness recrystallize the residue from ethyl acetate

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Add 13β-ethyl-3-methoxy-gona-2,5(10)-dien-17-one (12.9 g.) with stirring under nitrogen to methanol (300 cc.) containing 11N hydrochloric acid (20 cc) and water (13 cc.). Stir two hours and add sodium bicarbonate (21 g.) portionwise. Filter the mixture and evaporate and filtrate to dryness. Recrystallize the residue from ethyl acetate (75 cc.) to obtain the title compound (10 g.), m.p. 158°-161° C; ultraviolet absorption peak at 240 mμ (ε17,800); infrared absorption peaks at 5.78, 6.00, 6.17 μ. Filter the mixture evaporate Recrystallize the residue from ethyl acetate (75 cc.)

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Add 13β-ethyl-3-methoxy-gona-2,5(10)-dien-17-one (12.9 g.) with stirring under nitrogen to methanol (300 cc.) containing 11N hydrochloric acid (20 cc) and water (13 cc.). Stir two hours and add sodium bicarbonate (21 g.) portionwise. Filter the mixture and evaporate and filtrate to dryness. Recrystallize the residue from ethyl acetate (75 cc.) to obtain the title compound (10 g.), m.p. 158°-161° C; ultraviolet absorption peak at 240 mμ (ε17,800); infrared absorption peaks at 5.78, 6.00, 6.17 μ. Filter the mixture evaporate Recrystallize the residue from ethyl acetate (75 cc.)

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Add sodium borohydride (200 mg.) in ethanol (25 cc.) to 13β-ethyl-gon-4-en-3,17-dione (1 g.) in ethanol (50 cc.) at 8°. After 15 minutes add an excess of acetic acid and evaporate the solution to dryness under reduced pressure. Add water, collect the product in ether, and after this work up in the usual manner, recrystallize from a mixture of ether and pentane to obtain 13β-ethyl-17β-hydroxy-gon-4-en-3-one; ultraviolet absorption peak at 240 mμ (ε15,500); infrared absorption peaks at 2.94, 6.06, 6.23. evaporate the solution to dryness under reduced pressure Add water, collect the product in ether after this work up in the usual manner, recrystallize from a mixture of ether and pentane

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Add sodium borohydride (200 mg.) in ethanol (25 cc.) to 13β-ethyl-gon-4-en-3,17-dione (1 g.) in ethanol (50 cc.) at 8°. After 15 minutes add an excess of acetic acid and evaporate the solution to dryness under reduced pressure. Add water, collect the product in ether, and after this work up in the usual manner, recrystallize from a mixture of ether and pentane to obtain 13β-ethyl-17β-hydroxy-gon-4-en-3-one; ultraviolet absorption peak at 240 mμ (ε15,500); infrared absorption peaks at 2.94, 6.06, 6.23. evaporate the solution to dryness under reduced pressure Add water, collect the product in ether after this work up in the usual manner, recrystallize from a mixture of ether and pentane

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: —Pyridinium-toluenesulfonate (5.0 g) was added to a solution of 13-ethylgon-4-ene-3,17-dione [Hoffmann-La Roche and Co.; AG, DE 1806410 (1967); 100.0 g] in a mixture of ethanol (600 ml), dioxane (800 ml) and triethyl orthoformate (199 ml). After 4.5 h stirring at room temperature pyridine (100 ml) was added and the reaction mixture was poured into a saturated aqueous solution of sodium hydrogencarbonate. The product was extracted into ethyl acetate; the combined organic phases were washed with water and brine, dried over magnesium sulfate and concentrated under reduced pressure, to give 3-ethoxy-13-ethylgona-3,5-dien-17-one (146.3 g). The product was used in the following step without further purification. was added The product was extracted into ethyl acetate the combined organic phases were washed with water and brine dried over magnesium sulfate concentrated under reduced pressure

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 500 Mg. of 13β-ethyl-gon-4-en-3,17-dione produced in Example 135, was dissolved in 10 ml. of a benzene-ether solvent mixture (1:1) and added to a solution of 50 ml. of liquid ammonia containing 0.1 ml. of acetone and 0.5 g. of potassium acetylide. The reaction mixture was agitated at the ammonia boiling point for 2 hours and then the ammonia was evaporated at room temperature. The organic materials were extracted with ether and then the solvent was evaporated in vacuo. The residue was purified by chromatography over 50 g. of silica gel and on elution with a benzene-ethyl acetate mixture, afforded 13β-ethyl-17α-ethynyl-17-hydroxy-gon-4-en-3-one. the ammonia was evaporated at room temperature The organic materials were extracted with ether the solvent was evaporated in vacuo The residue was purified by chromatography over 50 g of silica gel and on elution with a benzene-ethyl acetate mixture

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Treat dl-13-ethyl-3-methoxygona-2,5(10)-dien-17-one with hydrochloric acid in aqueous methanol to obtain dl-13-ethylgon-4-ene-3,17-dione (25.6, 54% from dl-13-ethyl-3-methoxygona-2,5(10)-dien-17β-ol), m.p. 156°-157.5°; ultraviolet absorption peak in 95% ethanol at 240.5 mμ (15,900), infrared maxima (potassium bromide) at 5.77 μ, 5.98 μ . Recrystallize dl-13-ethylgon-4-ene-3,17-dione (1.0 g) three times from ethyl acetate to obtain 484 mg., 157°-159.5°; ultraviolet absorption peak (95% ethanol) at 240 mμ (ε17,200), infrared maxima (potassium bromide) at 5.77 μ, 5.98 μ.

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Heat 13β-ethyl-3-methoxy-17,17-ethylenedioxy-gona-2,5(10)-diene (0.1 g.) in glacial acetic acid (2.5 cc.) and water (1 cc.) on a steam bath for 20 minutes, bring finally to boiling and allow to cool. Add aqueous sodium bicarbonate to neturalize the solution and ether extract the product. Wash, dry and evaporate the ether extracts to furnish a residue (0.065 g.); crystallize from a mixture of acetone and light petroleum to obtain the title compound (0.01 g.), m.p. 154°-5°; ultraviolet absorption peak at 239 mμ (ε15,000); infrared absorption peaks at 5.75, 5.96 μ. to cool extract the product Wash dry evaporate the ether to furnish a residue (0.065 g.) crystallize from a mixture of acetone and light petroleum