Processes and intermediates for the preparations of Carboprost and Carboprost Tromethamine, and Carboprost Tromethamine prepared therefrom

A process for preparing Carboprost containing no more than 0.5% 15R-epimer, the process comprising the steps of:

• (a) preparing a compound of Formula 3 with a 15(S) selectivity greater than 50%,
• wherein P1 is H or a protecting group for hydroxy groups,
• wherein the compound of formula 3 is prepared by methylation of a compound of Formula 2a′, wherein P1 is H or a protecting group for hydroxy groups, with a methylation reagent to form the compound of Formula 3,
• wherein the methylation reagent is MeLi;
• (b) chromatographic separation of the compound of Formula 3 to remove 15(R)-epimer;
• and
• (c) hydrolysis of the compound of Formula 3, to form a compound of Formula 4:
• wherein P1 is H or a protecting group for hydroxy groups, and optionally performing a deprotecting reaction of the compound of Formula 4,
• when P1 is a protecting group for hydroxy groups, to form a compound of Formula 4, wherein P1 is H.