Processes for preparation of 9,11-epoxy steroids and intermediates useful therein

A process for the preparation of a compound corresponding to Formula II:

• wherein
• —A—A— represents the group —CHR4—CHR5— or —CR4═CR5—;
• R1 represents an alpha-oriented lower alkoxycarbonyl or hydroxycarbonyl radical;
• R3, R4 and R5 are independently selected from the group consisting of hydrogen, halo, hydroxy, lower alkyl, lower alkoxy, hydroxyalkyl, alkoxyalkyl, hydroxycarbonyl, cyano and aryloxy;
• and
• —B—B— represents the group —CHR6—CHR7— or an alpha- or beta-oriented group:
• where R6 and R7 are independently selected from the group consisting of hydrogen, halo, lower alkoxy, acyl, hydroxyalkyl, alkoxyalkyl, hydroxycarbonyl, alkyl, alkoxycarbonyl, acyloxyalkyl, cyano and aryloxy;
• and
• R8 and R9 are independently selected from the group consisting of hydrogen, hydroxy, halo, lower alkoxy, acyl, hydroxyalkyl, alkoxyalkyl, hydroxycarbonylalkyl, alkoxycarbonylalkyl, acyloxyalkyl, cyano and aryloxy, or R8 and
• R9 together comprise a carbocyclic or heterocyclic ring structure, or R8 or R9 together with R6 or R7 comprise a carbocyclic or heterocyclic ring structure fused to the pentacyclic D ring;
• the process comprising:
• alkylating a compound of Formula EI by hydrolysis followed by reaction with an alkylating reagent in the presence of a base, the compound of Formula El having the structure:
• wherein —A—A—, R3, R8, R9 and —B—B— are as defined above, and R17 is C1 to C4 alkyl.

A process for the preparation of a compound corresponding to Formula IIC:

• wherein
• —A—A— represents the group —CHR4—CHR5— or —CR4═CR5—;
• R1 represents an alpha-oriented lower alkoxycarbonyl or hydroxycarbonyl radical;
• R3, R4 and R5 are independently selected from the group consisting of hydrogen, halo, hydroxy, lower alkyl, lower alkoxy, hydroxyalkyl, alkoxyalkyl, hydroxycarbonyl, cyano and aryloxy;
• and
• —B—B— represents the group —CHR6—CHR7— or an alpha- or beta-oriented group:
• where R6 and R7 are independently selected from the group consisting of hydrogen, halo, lower alkoxy, acyl, hydroxyalkyl, alkoxyalkyl, hydroxycarbonyl, alkyl, alkoxycarbonyl, acyloxyalkyl, cyano and aryloxy;
• the process comprising:
• alkylating a compound of Formula E by hydrolysis followed by reaction with an alkylating reagent in the presence of a base, the compound of Formula E having the structure:
• wherein —A—A—, —B—B— and R3, are as defined above, and R17 is C1 to C4 alkyl.

A process for the preparation of a compound corresponding to Formula I:

• wherein
• —A—A— represents the group —CHR4—CHR5— or —CR4═CR5—;
• R3, R4 and R5 are independently selected from the group consisting of hydrogen, halo, hydroxy, lower alkyl, lower alkoxy, hydroxyalkyl, alkoxyalkyl, hydroxycarbonyl, cyano and aryloxy;
• R26 is C1 to C4 alkyl;
• and
• —B—B— represents the group —CHR6—CHR7— or an alpha- or beta-oriented group:
• where R6 and R7 are independently selected from the group consisting of hydrogen, halo, lower alkoxy, acyl, hydroxyalkyl, alkoxyalkyl, hydroxycarbonyl, alkyl, alkoxycarbonyl, acyloxyalkyl, cyano and aryloxy;
• and
• R80 and R90 are independently selected from R8 and R9, respectively, or R80 and R90 together form keto;
• R8 and R9 are independently selected from the group consisting of hydrogen, hydroxy, halo, lower alkoxy, acyl, hydroxyalkyl, alkoxyalkyl, hydroxycarbonylalkyl, alkoxycarbonylalkyl, acyloxyalkyl, cyano and aryloxy, or R8 and R9 together comprise a carbocyclic or heterocyclic ring structure, or R9 together with R6 or R7 comprise a carbocyclic or heterocyclic ring structure fused to the pentacyclic D ring;
• the process comprising:
• alkylating a compound of Formula A211 by reaction with an alkylating reagent in the presence of a base, the compound of Formula A211 having the structure:
• wherein —A—A—, —B—B—, R3, R80 and R90 are as defined above.

A process for the preparation of a compound corresponding to Formula IE:

• wherein
• —A—A— represents the group —CHR4—CHR5— or —CR4═CR5—;
• R3, R4 and R5 are independently selected from the group consisting of hydrogen, halo, hydroxy, lower alkyl, lower alkoxy, hydroxyalkyl, alkoxyalkyl, hydroxycarbonyl, cyano and aryloxy;
• R26 is C1 to C4 alkyl;
• and
• —B—B— represents the group —CHR6—CHR7— or an alpha- or beta-oriented group:
• where R6 and R7 are independently selected from the group consisting of hydrogen, halo, lower alkoxy, acyl, hydroxyalkyl, alkoxyalkyl, hydroxycarbonyl, alkyl, alkoxycarbonyl, acyloxyalkyl, cyano and aryloxy;
• the process comprising:
• alkylating a compound of Formula 211 by reaction with an alkylating reagent in the presence of a base, the compound of Formula 211 having the structure:
• wherein —A—A—, —B—B— and R3 are as defined above.