lithium;benzenethiolate

Conditions: temp:-15.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: —Vinylmagnesium chloride in tetrahydrofuran (2 M, 9.55 ml) was added dropwise to a mixture of (17β)-17-(acetyloxy)estra-4,6-dien-3-one (Example 3, step i; 3.0 g), copper(I) bromide-dimethyl sulfide complex (0.191 g), lithium bromide (0.083 g), and lithium thiophenoxide (0.96 ml of a 1 M solution in tetrahydrofuran), in dry tetrahydrofuran (10 ml), cooled to −15° C. After 25 min. stirring a saturated aqueous solution of ammonium chloride was added and the product extracted into ethyl acetate. The combined organic phases were concentrated under reduced pressure whereafter the residue was dissolved in acetone (100 ml) and treated with hydrochloric acid (4 M, 10 ml). After 30 min. stirring at room temperature, a saturated aqueous solution of sodium hydrogencarbonate was added. The product was extracted into ethyl acetate; the combined organic phases were washed with brine, dried over sodium sulfate and concentrated under reduced pressure, to give (7α,17β)-17-(acetyloxy)-7-ethenylestr-4-en-3-one (3.76 g). The product was used in the following step without further purification. was added the product extracted into ethyl acetate The combined organic phases were concentrated under reduced pressure whereafter the residue was dissolved in acetone (100 ml) treated with hydrochloric acid (4 M, 10 ml) a saturated aqueous solution of sodium hydrogencarbonate was added The product was extracted into ethyl acetate the combined organic phases were washed with brine dried over sodium sulfate concentrated under reduced pressure

Conditions: temp:60.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: In a 1L 3-neck flask, equipped with a mechanical stirrer, were mixed phenyl magnesium chloride (96.1 mL; 192 mmol; 2.00M in THF) and lithium thiophenoxide (211 mL; 211 mmol; 1.00M THF) under a blanket of nitrogen. This mixture was heated to 60° C. for 1 h, and then cooled to 0-5° C. with an ice bath. In a separate 150 mL flask, nickel acetylacetonate (“anhydrous”; 0.617 g; 2.40 mmol; 0.025 equiv.) was dissolved under nitrogen in anhydrous THF (100 mL). To this green solution was added trimethylphosphine (4.8 mL; 4.80 mmol; 1.00M in toluene; 0.05 equiv.) forming a blue solution. After stirring for 10 min, solid 4-cyanopyridine (10.0 g; 96.1 mmol; 1 equiv.) was added to the catalyst mixture forming a green solution. This solution was added via addition funnel to the PhMgCl/PhSLi reaction solution at a rate which maintained the reaction temperature below 15° C. After the addition was complete, the reaction was heated at 60° C. for 2 h. The reaction was then allowed to cool to room temperature, and was poured into 1M aqueous sodium citrate (500 mL). The organic layer was separated and the aqueous layer extracted three times with MTBE (265 mL each). The combined organic phase was extracted three times with 2N aqueous HCl (250 mL each) and this combined aqueous extract was basified to pH≈12 with 1N aqueous NaOH. This mixture was then extracted three times with MTBE (330 mL each) and the combined organic phase was dried over anhydrous magnesium sulfate. After filtration of the drying agent, solvent was removed in vacuo leaving 14.1 g (91% yield) of 4-phenylpyridine as a light yellow solid. GC analysis of the product showed it to be >95% pure. cooled to 0-5° C. with an ice bath forming a blue solution forming a green solution maintained the reaction temperature below 15° C After the addition the reaction was heated at 60° C. for 2 h to cool to room temperature The organic layer was separated the aqueous layer extracted three times with MTBE (265 mL each) The combined organic phase was extracted three times with 2N aqueous HCl (250 mL each) this combined aqueous extract This mixture was then extracted three times with MTBE (330 mL each) the combined organic phase was dried over anhydrous magnesium sulfate After filtration of the drying agent, solvent was removed in vacuo

Conditions: temp:-15.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: —Vinylmagnesium chloride in tetrahydrofuran (2 M, 9.55 ml) was added dropwise to a mixture of (17β)-17-(acetyloxy)estra-4,6-dien-3-one (Example 3, step i; 3.0 g), copper(I) bromide-dimethyl sulfide complex (0.191 g), lithium bromide (0.083 g), and lithium thiophenoxide (0.96 ml of a 1 M solution in tetrahydrofuran), in dry tetrahydrofuran (10 ml), cooled to −15° C. After 25 min. stirring a saturated aqueous solution of ammonium chloride was added and the product extracted into ethyl acetate. The combined organic phases were concentrated under reduced pressure whereafter the residue was dissolved in acetone (100 ml) and treated with hydrochloric acid (4 M, 10 ml). After 30 min. stirring at room temperature, a saturated aqueous solution of sodium hydrogencarbonate was added. The product was extracted into ethyl acetate; the combined organic phases were washed with brine, dried over sodium sulfate and concentrated under reduced pressure, to give (7α,17β)-17-(acetyloxy)-7-ethenylestr-4-en-3-one (3.76 g). The product was used in the following step without further purification. was added the product extracted into ethyl acetate The combined organic phases were concentrated under reduced pressure whereafter the residue was dissolved in acetone (100 ml) treated with hydrochloric acid (4 M, 10 ml) a saturated aqueous solution of sodium hydrogencarbonate was added The product was extracted into ethyl acetate the combined organic phases were washed with brine dried over sodium sulfate concentrated under reduced pressure

Conditions: temp:-15.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: —Vinylmagnesium chloride in tetrahydrofuran (2 M, 9.55 ml) was added dropwise to a mixture of (17β)-17-(acetyloxy)estra-4,6-dien-3-one (Example 3, step i; 3.0 g), copper(I) bromide-dimethyl sulfide complex (0.191 g), lithium bromide (0.083 g), and lithium thiophenoxide (0.96 ml of a 1 M solution in tetrahydrofuran), in dry tetrahydrofuran (10 ml), cooled to −15° C. After 25 min. stirring a saturated aqueous solution of ammonium chloride was added and the product extracted into ethyl acetate. The combined organic phases were concentrated under reduced pressure whereafter the residue was dissolved in acetone (100 ml) and treated with hydrochloric acid (4 M, 10 ml). After 30 min. stirring at room temperature, a saturated aqueous solution of sodium hydrogencarbonate was added. The product was extracted into ethyl acetate; the combined organic phases were washed with brine, dried over sodium sulfate and concentrated under reduced pressure, to give (7α,17β)-17-(acetyloxy)-7-ethenylestr-4-en-3-one (3.76 g). The product was used in the following step without further purification. was added the product extracted into ethyl acetate The combined organic phases were concentrated under reduced pressure whereafter the residue was dissolved in acetone (100 ml) treated with hydrochloric acid (4 M, 10 ml) a saturated aqueous solution of sodium hydrogencarbonate was added The product was extracted into ethyl acetate the combined organic phases were washed with brine dried over sodium sulfate concentrated under reduced pressure

Conditions: temp:-15.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: —Vinylmagnesium chloride in tetrahydrofuran (2 M, 159.2 ml) was added dropwise to a mixture of (17β)-17-(acetyloxy)estra-4,6-diene-3-one [Syntex, DE 1143199 (1963); 50.0 g], copper(I) bromide-dimethyl sulfide complex (3.18 g), lithium bromide (1.38 g), and lithium thiophenoxide (16 ml of a 1 M solution in tetrahydrofuran), in dry tetrahydrofuran (167 ml), cooled to −15° C. After 30 min. stirring a saturated aqueous solution of ammonium chloride was added and the product extracted into ethyl acetate. The combined organic phases were concentrated under reduced pressure whereafter the residue was dissolved in acetone (1000 ml) and treated with hydrochloric acid (4 M, 100 ml). After 30 min. stirring at room temperature, the mixture was poured into a saturated aqueous solution of sodium hydrogencarbonate. Part of the acetone was removed under reduced pressure and the product was extracted into ethyl acetate. The combined organic phases were washed with brine, dried over sodium sulfate and concentrated under reduced pressure, to give (7α,17β)-17-(acetyloxy)-7-ethenylestr-4-en-3-one (59.4 g). The product was used in the following step without further purification. was added the product extracted into ethyl acetate The combined organic phases were concentrated under reduced pressure whereafter the residue was dissolved in acetone (1000 ml) treated with hydrochloric acid (4 M, 100 ml) the mixture was poured into a saturated aqueous solution of sodium hydrogencarbonate Part of the acetone was removed under reduced pressure the product was extracted into ethyl acetate The combined organic phases were washed with brine dried over sodium sulfate concentrated under reduced pressure

Conditions: temp:60.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: In a 1 L 3-neck flask, equipped with a mechanical stirrer, were mixed phenyl magnesium chloride (96.1 mL; 192 mmol; 2.00 M in THF) and lithium thiophenoxide (211 mL; 211 mmol; 1.00 M THF) under a blanket of nitrogen. This mixture was heated to 60° C. for 1 h, and then cooled to 0-5° C. with an ice bath. In a separate 150 mL flask, nickel acetylacetonate (“anhydrous”; 0.617 g; 2.40 mmol; 0.025 equiv.) was dissolved under nitrogen in anhydrous THF (100 mL). To this green solution was added trimethylphosphine (4.8 mL; 4.80 mmol; 1.00 M in toluene; 0.05 equiv.) forming a blue solution. After stirring for 10 min, solid 4-cyanopyridine (10.0 g; 96.1 mmol; 1 equiv.) was added to the catalyst mixture forming a green solution. This solution was added via addition funnel to the PhMgCl/PhSLi reaction solution at a rate which maintained the reaction temperature below 15° C. After the addition was complete, the reaction was heated at 60° C. for 2 h. The reaction was then allowed to cool to room temperature, and was poured into 1M aqueous sodium citrate (500 mL). The organic layer was separated and the aqueous layer extracted three times with MTBE (265 mL each). The combined organic phase was extracted three times with 2 N aqueous HCl (250 mL each) and this combined aqueous extract was basified to pH 12 with 1 N aqueous NaOH. This mixture was then extracted three times with MTBE (330 mL each) and the combined organic phase was dried over anhydrous magnesium sulfate. After filtration of the drying agent, solvent was removed in vacuo leaving 14.1 g (91% yield) of 4-phenylpyridine as a light yellow solid. GC analysis of the product showed it to be >95% pure. In a 1 L 3-neck flask, equipped with a mechanical stirrer cooled to 0-5° C. with an ice bath forming a blue solution forming a green solution maintained the reaction temperature below 15° C After the addition the reaction was heated at 60° C. for 2 h to cool to room temperature The organic layer was separated the aqueous layer extracted three times with MTBE (265 mL each) The combined organic phase was extracted three times with 2 N aqueous HCl (250 mL each) this combined aqueous extract This mixture was then extracted three times with MTBE (330 mL each) the combined organic phase was dried over anhydrous magnesium sulfate After filtration of the drying agent, solvent was removed in vacuo

Conditions: temp:60.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: In a 1L 3-neck flask, equipped with a mechanical stirrer, were mixed phenyl magnesium chloride (96.1 mL; 192 mmol; 2.00M in THF) and lithium thiophenoxide (211 mL; 211 mmol; 1.00M THF) under a blanket of nitrogen. This mixture was heated to 60° C. for 1 h, and then cooled to 0-5° C. with an ice bath. In a separate 150 mL flask, nickel acetylacetonate (“anhydrous”; 0.617 g; 2.40 mmol; 0.025 equiv.) was dissolved under nitrogen in anhydrous THF (100 mL). To this green solution was added trimethylphosphine (4.8 mL; 4.80 mmol; 1.00M in toluene; 0.05 equiv.) forming a blue solution. After stirring for 10 min, solid 4-cyanopyridine (10.0 g; 96.1 mmol; 1 equiv.) was added to the catalyst mixture forming a green solution. This solution was added via addition funnel to the PhMgCl/PhSLi reaction solution at a rate which maintained the reaction temperature below 15° C. After the addition was complete, the reaction was heated at 60° C. for 2 h. The reaction was then allowed to cool to room temperature, and was poured into 1M aqueous sodium citrate (500 mL). The organic layer was separated and the aqueous layer extracted three times with MTBE (265 mL each). The combined organic phase was extracted three times with 2N aqueous HCl (250 mL each) and this combined aqueous extract was basified to pH≈12 with 1N aqueous NaOH. This mixture was then extracted three times with MTBE (330 mL each) and the combined organic phase was dried over anhydrous magnesium sulfate. After filtration of the drying agent, solvent was removed in vacuo leaving 14.1 g (91% yield) of 4-phenylpyridine as a light yellow solid. GC analysis of the product showed it to be >95% pure. cooled to 0-5° C. with an ice bath forming a blue solution forming a green solution maintained the reaction temperature below 15° C After the addition the reaction was heated at 60° C. for 2 h to cool to room temperature The organic layer was separated the aqueous layer extracted three times with MTBE (265 mL each) The combined organic phase was extracted three times with 2N aqueous HCl (250 mL each) this combined aqueous extract This mixture was then extracted three times with MTBE (330 mL each) the combined organic phase was dried over anhydrous magnesium sulfate After filtration of the drying agent, solvent was removed in vacuo

Conditions: temp:-15.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: —Vinylmagnesium chloride in tetrahydrofuran (2 M, 9.55 ml) was added dropwise to a mixture of (17β)-17-(acetyloxy)estra-4,6-dien-3-one (Example 3, step i; 3.0 g), copper(I) bromide-dimethyl sulfide complex (0.191 g), lithium bromide (0.083 g), and lithium thiophenoxide (0.96 ml of a 1 M solution in tetrahydrofuran), in dry tetrahydrofuran (10 ml), cooled to −15° C. After 25 min. stirring a saturated aqueous solution of ammonium chloride was added and the product extracted into ethyl acetate. The combined organic phases were concentrated under reduced pressure whereafter the residue was dissolved in acetone (100 ml) and treated with hydrochloric acid (4 M, 10 ml). After 30 min. stirring at room temperature, a saturated aqueous solution of sodium hydrogencarbonate was added. The product was extracted into ethyl acetate; the combined organic phases were washed with brine, dried over sodium sulfate and concentrated under reduced pressure, to give (7α,17β)-17-(acetyloxy)-7-ethenylestr-4-en-3-one (3.76 g). The product was used in the following step without further purification. was added the product extracted into ethyl acetate The combined organic phases were concentrated under reduced pressure whereafter the residue was dissolved in acetone (100 ml) treated with hydrochloric acid (4 M, 10 ml) a saturated aqueous solution of sodium hydrogencarbonate was added The product was extracted into ethyl acetate the combined organic phases were washed with brine dried over sodium sulfate concentrated under reduced pressure