Back to results
US 10,112,970 B2Granted
Process for the preparation of 17-desoxy-corticosteroids
AssigneeTaro Pharmaceutical Industries Ltd.
InventorsSimon Cherniak, Rosa Cyjon, Ilana Ozer, Igor Nudelman
Life of this patent
Estimating the term…
Abstract
The present invention provides an improved process for the preparation of 17-desoxy corticosteroid derivatives in a single chemical step by reacting the 17-hydroxy starting material with an excess of Trimethylsilyl Iodide. The present invention is specifically advantageous in preparing 17-desoxy corticosteroid derivatives having one or more halogen groups at positions 2, 6, 7 or 9 of the corticosteroid such as Clocortolone of Desoximetasone.
Claims33
A process for preparing a compound of Formula I
- in which R1 is OH and R2 is H, or R1 and R2 form together a double bond with O, R3 is H and R4 is CH3, or R3 is CH3 and R4 is H, and wherein at least one of X1-5 is independently Cl, Br or F, and all other of X1-5 are H, comprising the steps of:
- (a) reacting a compound of formula II
- in which R1-R4 and X1-5 are as defined in Formula I with Trimethylsilyl Iodide in a solution of an aprotic solvent, wherein the molar ratio between Trimethylsilyl Iodide and the compound of Formula II is about 2:1 to about 10:1;
- (b) quenching the reaction of step (a);
- (c) extracting the compound of Formula I from the solution of step (b) using an organic solvent to yield an organic layer comprising the compound of Formula I;
- and
- (d) isolating the compound of Formula I from the organic layer of step (c).
4 more elements
A method of preparing Clocortolone of Formula III
- comprising the steps of:
- a) reacting a 17-hydroxy epoxide of Formula IV
- with a stereo-selective fluorinating agent to stereo-selectively form a 17-hydroxy epoxide 6α-fluorinated compound of Formula V
- wherein R1 and R2 are OC(O)—Rd, each of Rd may be the same or different and is independently selected from (C1-4) alkyl;
- b) hydrolyzing the compound of formula V with an alkaline carbonate in a first organic solvent to form a compound of formula VI;
- c) opening the epoxide of the compound of formula VI by a reaction with hydrogen chloride to form a compound of formula VII;
- d) reacting the compound of formula VII with Trimethylsilyl Iodide in a solution of an aprotic solvent, wherein the molar ratio between Trimethylsilyl Iodide and the compound of Formula VII is about 2:1 to about 10:1, to form a compound of formula III;
- and
- e) quenching the reaction of step (d) and isolating the compound of Formula III.
6 more elements
Dependencies are inferred from the claim text.