Process for preparation of 13,14-dihydro-pgf2 alpha derivatives

A compound of the general formula (VI)

• wherein
• LG represents a halogen, an alkylsulfonyloxy, an alkylarylsulfonyloxy, or a arylsulfonyloxy group, and R3 represents H or a hydroxyl protecting group;
• or LG and R3 represent a chemical bond and/or taken together with the atoms to which they are attached and with an —S(O)— or an —SO2— group form a cyclosulfite or a cyclosulfate;
• or LG and R3 represent chemical bonds and/or taken together with the atoms to which they are attached form an epoxide;
• Z represents H, a methyl or a phenyl, optionally substituted by a C1-3-alkyl, a C1-3-alkoxy or at least one halogen atom;
• n represents an integer from 0 to 6;
• and
• the compound has an R or S chiral configuration at the carbon atom substituted by —OR3.

A process for the preparation of a compound of the general formula (VI)

• wherein
• LG represents a halogen, an alkylsulfonyloxy, an alkylarylsulfonyloxy, or a arylsulfonyloxy group, and R3 represents H or a hydroxyl protecting group;
• or LG and R3 represent a chemical bond and/or taken together with the atoms to which they are attached and with an —S(O)— or an —SO2— group form a cyclosulfite or a cyclosulfate;
• or LG and R3 represent chemical bonds and/or taken together with the atoms to which they are attached form an epoxide;
• Z represents H, a methyl or a phenyl, optionally substituted by a C1-3-alkyl, a C1-3-alkoxy or at least one halogen atom;
• n represents an integer from 0 to 6;
• and
• the compound has an R or S chiral configuration at the carbon atom substituted by —OR3.
• comprising the steps of:
• (a) converting a 2(S)- or 2(R)-4-phenyl-1,2-alkyldiol of the formula HO—CH2—CH(OH)—(CH2)n-Z, wherein Z represents H, a methyl or a phenyl, optionally substituted by a C1-3-alkyl, a C1-3-alkoxy or at least one halogen atom;
• and n represents an integer from 0 to 6;
• to a compound of the general formula (VI)
• wherein R3 is H;
• LG is —OSO2—Ar;
• Z represents H, a methyl or a phenyl, optionally substituted by a C1-3-alkyl, a C1-3-alkoxy or at least one halogen atom;
• n represents an integer from 0 to 6;
• and Ar represents substituted or unsubstituted aryl or heteroaryl;
• (b) converting the compound obtained in step (a) to a compound of the general formula (VI)
• wherein R3 is a hydroxyl protecting group;
• LG is —OSO2—Ar;
• Z represents H, a methyl or a phenyl, optionally substituted by a C1-3-alkyl, a C1-3-alkoxy or at least one halogen atom;
• n represents an integer from 0 to 6;
• and Ar represents substituted or unsubstituted aryl or heteroaryl;
• (c) converting the compound obtained in step (b) to a compound of the general formula (VI)
• wherein R3 is a hydroxyl protecting group;
• LG is a halogen;
• Z represents H, a methyl or a phenyl, optionally substituted by a C1-3-alkyl, a C1-3-alkoxy or at least one halogen atom;
• and n represents an integer from 0 to 6;
• and
• (d) converting the compound obtained in step (c) to a compound of the general formula (VI)
• wherein LG and R3 represent chemical bonds and taken together with the atoms to which they are attached form an epoxide;
• Z represents H, a methyl or a phenyl, optionally substituted by a C1-3-alkyl, a C1-3-alkoxy or at least one halogen atom;
• and n represents an integer from 0 to 6.

A process for the preparation of a compound of the general formula (VI)

• wherein
• LG represents a halogen, an alkylsulfonyloxy, an alkylarylsulfonyloxy, or a arylsulfonyloxy group, and R3 represents H or a hydroxyl protecting group;
• or LG and R3 represent a chemical bond and/or taken together with the atoms to which they are attached and with an —S(O)— or an —SO2— group form a cyclosulfite or a cyclosulfate;
• or LG and R3 represent chemical bonds and/or taken together with the atoms to which they are attached form an epoxide;
• Z represents H, a methyl or a phenyl, optionally substituted by a C1-3-alkyl, a C1-3-alkoxy or at least one halogen atom;
• n represents an integer from 0 to 6;
• and
• the compound has an R or S chiral configuration at the carbon atom substituted by —OR3.
• comprising the steps of:
• (a) converting a 2(S)- or 2(R)-4-phenyl-1,2-alkyldiol of formula HO—CH2—CH(OH)—(CH2)n-Z, wherein Z represents H, a methyl or a phenyl, optionally substituted by a C1-3-alkyl, a C1-3-alkoxy or at least one halogen atom;
• and n represents an integer from 0 to 6;
• to a compound of the general formula (VI)
• wherein LG and R3 represent a chemical bond and taken together with the atoms to which they are attached and with an —S(O)— group form a cyclosulfite;
• and
• (b) converting the compound obtained in step (a) to a compound of the general formula (VI)
• wherein LG and R3 represent a chemical bond and taken together with the atoms to which they are attached and with an —SO2— group form a cyclosulfate.