Process for the preparation of a chiral prostaglandin enol intermediate and intermediate compounds useful in the process

A compound selected from:

• a compound of formula 16-(R,S)-10:
• a compound of formula 16-(R)-10:
• a compound of formula 16-(S)-10:
• and
• a compound of formula 15-(R,S), 16-(R)-11:

A process for the fractional crystallization of the compound of formula 16-(R,S)-10,

• using a solvent selected from C1-3 alcohols, tert-butyl methyl ether and their mixtures;
• comprising
• (a) suspending the compound of formula 16-(R,S)-10 in the solvent, refluxing the suspension, followed by cooling the mixture to 25-35° C. and stirring while maintaining the temperature, followed by filtering, washing and drying the precipitated crystals, thereby obtaining crystals Kr1;
• (b) seeding the filtrate combined with the washing liquid with crystals of the compound of formula 16-(R)-10, cooling the suspension to 0-5° C. and stirring while maintaining the temperature, followed by filtering, washing and drying the precipitated crystals, thereby obtaining crystals Kr2;
• and
• optionally
• (c) suspending the previously filtered crystals Kr1 in the filtrate combined with the washing liquid, refluxing the suspension, followed by cooling the mixture to 25-35° C. and stirring while maintaining the temperature, followed by filtering, washing and drying the precipitated crystals, thereby obtaining crystals Kr3;
• and
• (d) seeding the filtrate combined with the washing liquid with crystals of the compound of formula 16-(R)-10, cooling to 0-5° C. and stirring while maintaining the temperature, followed by filtering, washing and drying the precipitated crystals, thereby obtaining crystals Kr4,
• wherein compound of formula 16-(S)-10 is obtained as crystals Kr1 and Kr3 in step (a) and in optional step (c), and compound of formula 16-(R)-10 is obtained as crystals Kr2 and Kr4 in step (b) and in optional step (d),
• and optionally,
• recrystallizing the obtained crystals from a solvent selected from C1-3 alcohols, tert-butyl methyl ether and their mixtures;
• or from a mixture of said solvents with dichloromethane.

A process for the preparation of the compound of formula 16-(S)-10,

• comprising
• (a) suspending a compound of formula 16-(R,S)-10 in a solvent selected from C1-3 alcohols, tert-butyl methyl ether and their mixtures, refluxing the suspension, followed by cooling the mixture to 25-35° C. and stirring while maintaining the temperature, followed by filtering, washing and drying the precipitated crystals, thereby obtaining crystals Kr1;
• and optionally
• (b) seeding the filtrate combined with the washing liquid with crystals of the compound of formula 16-(R)-10, cooling the suspension to 0-5° C. and stirring while maintaining the temperature, followed by filtering the precipitated crystals;
• and
• (c) suspending the previously filtered crystals Kr1 in the filtrate, refluxing the suspension, followed by cooling the mixture to 25-35° C. and stirring while maintaining the temperature, followed by filtering, washing and drying the precipitated crystals, thereby obtaining crystals Kr3;
• and optionally, recrystallizing the obtained crystals Kr1 or Kr3 from a mixture of dichloromethane and a solvent selected from C1-3 alcohols, tert-butyl methyl ether and their mixtures;
• thereby obtaining the compound of formula 16-(S)-10.