Novel intermediates and an improved process for producing the compound (3.beta.,5.alpha.)-3-hydroxycholest-8(14)-en-15-one

A process for producing (3.beta.,5.alpha.)-3-hydroxycholest-8(14)en-15-one, which comprises the steps of:

• (a) dissolving 5,7-cholestadien-3.beta.-ol benzoate in chloroform, purging with nitrogen as the solution is e cooled to --65.degree. C. in dry ice-acetone, adding an acid for an effective time while maintaining the below -60.degree. C., then treating the solution with ice and ammonium hydroxide, separating the chloroform layer and adding it to pyridine, washing the chloroform layer with water, collecting the compound (3.beta.,5.alpha.) cholesta-7,14-dien-3-ol benzoate by filtration, which is then washed with water and dried, then
• (b) treating a suspension of (3.beta.,5.alpha.)cholesta-7,14-dien-3-ol benzoate and sodium bicarbonate in t-butyl methyl ether with a solution of a peracid in an organic solvent at 0.degree. C. to 20.degree. C. for an effective time, then treating the organic mixture with water and collecting the compound (3.beta.,5.alpha.,15.alpha.)-14,15-epoxycholest-7-en-3-ol benzoate by filtration at about 10.degree. C., washing the solid with an effective amount of methanol and recrystallizing the crude product from toluene:heptane (1:2) at an effective temperature, then
• (c) the recrystallized epoxide is stirred in acetone at 22.degree. C. to 26.degree.0 C., under nitrogen, and is treated with a catalytic amount of a protic acid for an effective time, then the mixture is treated with excess water at about 19.degree. C. for an effective time and the crude product (3.beta.,5.alpha.)-3-(benzoyloxy)cholest-8(14)en-15-one is collected by filtration, washed with water and dried in vacuo, then
• (d) a stirred mixture of the preceding crude product is treated for an effective time with (1) potassium carbonate in a protic solvent and heated at reflux, or (2) perchloric acid in n-propanol or ethanol at reflux, or (3) potassium hydroxide or sodium hydroxide in methanol at room temperature to give the desired product (3.beta.,5.alpha.)-3-hydroxycholest-8(14)en-15-one which is recrystallized from methanol, water and heptane at an effective chilling temperature for an effective time and is collected by filtration and washed with methanol.

A process for producing (3.beta.,5.alpha.)-3-hydroxycholest-8(14)en-15-one, which comprises:

• (a) dissolving 5,7-cholestadien-3? -ol benzoate in chloroform, purging with nitrogen as the solution is cooled to -65.degree. C. in dry ice-acetone adding an acid for an effective time while maintaining the temperature below -60.degree. C., then treating the solution with ice and ammonium hydroxide, separating the chloroform layer and adding it to pyridine, washing the chloroform layer with water, collecting the compound (3.beta.,5.alpha.)cholesta-7,14-dien-3-ol benzoate by filtration, which is then washed with water and dried, then
• (b) treating a suspension of (3.beta.,5.alpha.)cholesta-7,14-dien-3-ol benzoate and sodium bicarbonate in t-butyl methyl ether with a solution of a peracid in an organic solvent at 0.degree. to 20.degree. C. for an effective time, then treating the organic mixture with water and collecting the compound (3.beta.,5.alpha.,15.alpha.)-14,15-epoxycholest-7-en-3-ol benzoate by filtration at about 10.degree. C., washing the solid with an effective amount of methanol and recrystallizing the crude product from toluene:heptane (1:2) at an effective temperature, then
• (c) treating the epoxide (3.beta.,5.alpha.,15.alpha.)-14,15-epoxycholest-7-en-3-ol benzoate with a catalytic amount of a protic acid in acetone at a controlled temperature of about 15.degree. C. to about 22.degree. C. for 3 hours to the novel intermediate compound (3.beta.,b 5.alpha.)-3-(benzoyloxy)-cholest-7-en-15-one, then
• (d) further treating the preceding compound with a catalytic amount of a protic acid in acetone at about 23.degree.-26.degree. C. for 2 hours to give the precursor compound (3.beta.,5.alpha.)-3-(benzoyloxy)cholest-8(14)en-15-one which is then treated for an effective time with (1) potassium carbonate in a protic solvent and heated at reflux, or (2) perchloric acid in n-propanol or ethanol at reflux, or (3) potassium hydroxide or sodium hydroxide in methanol at room temperature to provide the subject compound (3.beta.,5.alpha.)-3-hydroxycholest-8(14)en-15-one which is recrystallized from methanol, water and heptane at an effective chilling temperature for an effective time and is collected by filtration and washed with methanol;
• or
• (e) alternatively, heating a suspension of the novel intermediate compound of step (c), (3.beta.,5.alpha.)-3-(benzoyloxy) cholest-7-en-15-one in a mixture of ethanol, sulfuric acid and water at the reflux temperature for an effective time, then recrystallizing the subject compound (3.beta.,5.alpha.)-3-hydroxycholest-8(14)en-15-one from methanol, heptane and water at an effective temperature for an effective time.

A process for producing (3.beta.,5.alpha.,7.alpha.,15.alpha.)-7-methoxycholest-8(14)ene-3, 15-diol 3-benzoate which comprises the steps of:

• (a) dissolving 5,7-cholestadien-3.beta.-ol benzoate in chloroform, purging with nitrogen as the solution is cooled to -65.degree. C. in dry ice-acetone, adding an acid for an effective time while maintaining the temperature below -60.degree. C., then treating the solution with ice and ammonium hydroxide, separating the chloroform layer and adding it to pyridine, washing the chloroform layer with water, and collecting the compound (3.beta.,5.alpha.)-cholesta-7,14-dien-3-ol benzoate by filtration, which is then washed with water and dried, then
• (b) treating a suspension of (3.beta.,5.alpha.)cholesta-7,14-dien-3-ol benzoate and sodium bicarbonate in t-butyl methyl ether with a solution of a peracid in an organic solvent at 0.degree. C. for an effective time, then treating the organic mixture with water and collecting the compound (3.beta.,b 5.alpha.,15.alpha.)-14,15-epoxycholest-7-en-3-ol benzoate by filtration at about 10.degree. C., washing the solid with an effective amount of methanol and recrystallizing the crude product from toluene:heptane (1:2) at an effective temperature, then
• (c) adding the epoxide to 1:1 dichloromethane:
• methanol containing a catalytic amount of a protic acid and heating the mixture at the reflux temperature for an effective time, then cooling the mixture and evaporating the solvents in vacuo to obtain the novel intermediate compound (3.beta.,5.alpha.,7.alpha.,15.alpha.)-7-methoxy-cholest8(14)ene-3 ,15-diol 3-benzoate, and recrystallizing the product from hexane.

A process for producing (3.beta.,5.alpha.)-3(benzoyloxy) cholest-7-en-15-one which comprises the steps of:

• (a) dissolving 5,7-cholestadien-3.beta.-ol benzoate in chloroform, purging with nitrogen as the solution is cooled to -65.degree. C. in dry ice-acetone, adding an acid for an effective time while maintaining the temperature below -60.degree. C., then treating the solution with ice and ammonium hydroxide, separating the chloroform layer and adding it to pyridine, washing the chloroform layer with water, and collecting the compound (3.beta.,5.alpha.)cholesta-7,14-dien-3-ol benzoate by filtration, which is then washed with water and dried, then
• (b) treating a suspension of (3.beta.,5.alpha.)cholesta-7,14-dien-3-ol benzoate and sodium bicarbonate in t-butyl methyl ether with a solution of a peracid in an organic solvent at 0.degree. C. to 20.degree. C. for an effective time, then treating the organic mixture with water and collecting the compound (3.beta.,5.alpha.,15.alpha.)-14,15-epoxycholest-7-en-3-ol benzoate by filtration at about 10.degree. C., washing the solid with an effective amount of methanol and recrystallizing the crude product from toluene:heptane (1:2) at an effective temperature, then
• (c) treating the epoxide with a catalytic amount of a protic acid in acetone at a controlled temperature of about 15.degree. C. to about 22.degree. C. for 3 hours to give the novel intermediate compound (3.beta.,5.alpha.)-3-(benzoyloxy)cholest-7-en-15-one.