Process and new intermediates for the preparation of 11-methylene steroids
AssigneeCrystal Pharma, S.A.U.
InventorsCelso Miguel Sandoval Rodríguez, Ignacio Herráiz Sierra, Ivano Messina, Jesús Miguel Iglesias Retuerto
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Abstract
A process for the preparation of 11-methylene steroids from di-keto steroids involves selective olefination of the ketone at position 11 of the di-keto steroids. The resulting 11-methylene steroid products can be used as intermediates in the preparation of the synthetic steroids, Etonogestrel and Desogestrel, as well as other pharmaceutically active agents.
Claims12
A process for the preparation of a compound of formula (I), or a solvate thereof
- wherein
- X represents H or it forms together with the carbon atom to which it is bonded a ketone protecting group;
- Y together with the carbon atom to which it is bonded represents C═CH2 or C(OH)CH2Z, wherein Z is selected from H and SiR′3 wherein each R′ is independently selected from C1-C6 alkyl and C6-C10 aryl;
- R6 is selected from H, C1-C6 alkyl and halogen;
- R10 is selected from H, C1-C6 alkyl and halogen, or is absent when there is a double bond between C1 and C10;
- R13 is selected from H and C1-C6 alkyl;
- R16 is selected from H, C1-C6 alkyl and halogen;
- - - - is a single or double bond;
- which comprises reacting a compound of formula (II) or a solvate thereof
- wherein X, R6, R10, R13, R16, and - - - have the meanings defined above;
- with a compound of formula (III)
- wherein Z is selected from H and SiR′3 wherein each R′ is independently selected from C1-C6 alkyl and C6-C10 aryl and M is selected from Li, MgBr, MgCl and Mgl.
A process for the preparation of Desogestrel, Etonogestrel, or a solvate thereof, the process comprising:
- preparing a compound of formula (I) or a solvate thereof
- wherein
- X represents H or it forms together with the carbon atom to which it is bonded a ketone protecting group;
- Y together with the carbon atom to which it is bonded represents C═CH2 or C(OH)CH2Z, wherein Z is selected from H and SiR′3 wherein each R′ is independently selected from C1-C6 alkyl and C6-C10 aryl;
- R6 is selected from H, C1-C6 alkyl and halogen;
- R10 is selected from H, C1-C6 alkyl and halogen, or is absent when there is a double bond between C1 and C10;R13 is selected from H and C1-C6 alkyl;
- R16 is selected from H, C1-C6 alkyl and halogen;
- - - - is a single or double bond;
- by reacting a compound of formula (II) or a solvate thereof
- wherein X, R6, R10, R13, R16, and - - - have the meanings defined above;
- with a compound of formula (III)
- wherein Z is selected from H and SiR′3 wherein each R′ is independently selected from C1-C6 alkyl and C6-C10 aryl and M is selected from Li, MgBr, MgCI and MgI;
- and
- converting the compound of formula (I), or a solvate thereof to Desogestrel, Etonogestrel, or a solvate thereof.
Dependencies are inferred from the claim text.